Materials for use in ophthalmic applications and methods

ABSTRACT

A lens body comprising at least one form of boronic acid, boronic ester or boronic anhydride is provided. The lens body is contacted with a solution comprising at least one form of TRIS. A contact lens package including the contact lens, and methods of producing and using the contact lens, are also provided.

This application is a National Stage Application of PCT/US2010/049601,filed Sep. 21, 2010, which claims priority to U.S. Provisional PatentApplication No. 61/244,496, filed Sep. 22, 2009.

This application claims the benefit under 35 U.S.C. §119(e) of priorU.S. Provisional Patent Application No. 61/244,496, filed Sep. 22, 2009,which is incorporated in its entirety by reference herein.

FIELD OF THE INVENTION

The present invention relates to medical devices, compositions forforming such devices, and their use in ophthalmic applications such ascontact lens materials. In particular, the present invention relates tohydrogel contact lenses. The present invention also relates to packagingsystems including these lenses and methods of producing the lenses.

BACKGROUND

Although conventional hydrophilic polymer or hydrogel lenses are usefuland effective, some problems do present themselves, from time to time.For example, conventional hydrophilic contact lenses can be associatedwith lens wearer discomfort and/or eye irritation, which can result inthe lens wearer perceiving that his/her eye is dry. “Dry eye” phenomenonhas been treated by lens wearers with eye drops and/or lubricants.

Silicone hydrogel contact lenses are a commonly used type of contactlenses. Silicone hydrogels generally have higher oxygen permeabilitiesthan conventional hydrogel contact lenses. In addition, siliconehydrogels typically have more hydrophobic materials than conventionalhydrogel contact lenses, and therefore, additional processing steps orformulation ingredients are necessary to produce contact lenses withwettable surfaces compared to conventional hydrogel contact lenses.

Producing wettable silicone hydrogel contact lenses while addressingcommercial realities, such as low costs of goods, good clinicalperformance, and high processability, remains a challenge.

SUMMARY

The present contact lenses comprise lens bodies that comprise a reactionproduct of a polymerizable composition. A lens body of a contact lenshas a lens surface, such as an anterior lens surface or a posterior lenssurface. A first polyhydric alcohol is present on at least the lenssurface of the lens body. In one example, the first polyhydric alcoholcomprises a polyhydric alcohol with a backbone comprising at least threecarbon atoms, the at least three carbon atoms bonded in a chain as aright carbon atom bonded to a center carbon atom, the center carbon atombonded to a left carbon atom, wherein one and only one hydroxyl group isbonded to the right carbon atom, a hydroxyl group is not bonded to thecenter carbon atom, and one and only one hydroxyl group is bonded to theleft carbon atom. In another example, the first polyhydric alcoholcomprises a 1,3 diol (i.e., a diol with one hydroxyl group bonded toeach of the 1^(st) and 3^(rd) carbons in the chain). In another example,the first polyhydric alcohol comprises a 1,3 polyol (i.e., a polyhydricalcohol with more than two pendant hydroxyl groups, one and only one ofwhich is bonded to 1^(st) carbon in the chain and another one and onlyone of which is bonded to the 3^(rd) carbon in the chain, where the2^(nd) carbon in the chain does not have a hydroxyl group bonded to it).In another example, the polyhydric alcohol comprises a polyhydricalcohol with at least five pendant hydroxyl groups. In yet anotherexample, the polyhydric alcohol comprises a polyhydric alcohol with atleast five pendant hydroxyl groups, wherein two of the hydroxyl groupsare in the 1 and 3 positions on the carbon chain (i.e, a 1,3 polyol withat least 5 pendant hydroxyl groups). The polymerizable compositioncomprises at least one hydrophilic monomer, at least one crosslinkingagent that crosslinks the at least one hydrophilic monomer duringpolymerization to form a first polymer component, and at least oneophthalmically acceptable acid. The ophthalmically acceptable acid canbe distributed as a portion of the first polymer component, as a secondpolymer component, or both, in the reaction product within the lens bodyand at a lens surface thereof. The lens surface can have an advancingcontact angle of less than 100° and/or a water break up time (WBUT) ofgreater than five seconds, which are maintained following in vitrotesting for a duration of at least six hours. The ophthalmicallyacceptable acid can be used in a silicone hydrogel lens formulation or asilicone-free hydrogel lens formulation.

It has been found that the inclusion of at least one ophthalmicallyacceptable acid in a polymerizable composition used to produce a contactlens body provides a lens structure having at least a surface to which apolyhydric alcohol (polyol), such as a 1,3 polyol with at least fivehydroxyl (—OH) groups, can be attached. As the ophthalmically acceptableacid can be immobilized chemically, physically, or both chemically andphysically, in the lens body, including at least at a wetting portion ata surface of the lens body, the acid (or at least a portion, orsignificant portion) is not extracted or washed out during typicalmanufacturing, storage, and/or wear conditions (e.g., at least 90% byweight of the acid present when the lens is formed remains afterwards,such as from 90 wt % to 100 wt %, 95 wt % to 99.99 wt %, 97 wt % to 99wt %, 98 wt % to 99 wt %). It has been found that even a relativelysmall amount of ophthalmically acceptable acid provided in the lens bodyand on at least the lens surface is sufficient to interact (e.g., graftto, react, bond, or otherwise attach) with a polyol, e.g., a polyol withat least five hydroxyl groups, to achieve a wettable surface. As theimmobilized ophthalmically acceptable acid remains present in the lensbody and at lens surfaces thereof during use, the polyol also can remainpresent on at least the surface of the lens body for an extended periodof time after removal of the lens from a wetting solution or aqueoussolution and during use (wear) of the lens. The contact lens can show ahigh level of wettability based on in vitro tests over extended periodsof time. These contact lenses also can be recharged after a period ofuse by soaking the lenses in a solution of a polyol, such as a polyolwith at least five hydroxyl groups, such as by soaking overnight at roomtemperature. Further, the contact lenses made with the present lensformulations do not require extraction with organic solvents, aqueoussolutions of organic solvents, or water, although they can be extractedin this manner or can be hydrated in an aqueous solution or water priorto sterilizing, such as autoclaving. For example, a contact lens, asdescribed herein, can be separated from a lens mold (delensed) andplaced in a contact lens package without requiring an intermediatewashing step to remove extractable material from the lens body. Thus,the contact lens can be provided in an aqueous liquid in the lenspackage. The aqueous liquid may be a packaging solution. Optionally,however, a contact lens could be washed prior to providing the contactlens in the packaging solution. After providing the contact lens in apackaging solution, the package can be closed or sealed, and sterilized.

An example of a contact lens, as described herein, comprises a lens bodythat comprises a reaction product of a polymerizable compositioncomprising at least one hydrophilic monomer, at least one crosslinkingagent, and at least one ophthalmically acceptable acid. A polyol presentat least on a lens surface of the lens body can be polyvinyl alcohol,such as one with at least five hydroxyl groups. The present hydrogellenses, formed or treated or recharged with a polyol, like a polyvinylalcohol, can maintain good wettability for up to 48 hours or more. Itfurther has been found that the use of higher molecular weight forms ofpolyvinyl alcohol such as, for example, those with weight averagemolecular weights of from about 100,000 Daltons and above, can maintainthe lens in a wettable state for longer durations after the lens hasbeen removed from a solution containing the higher molecular polyvinylalcohol as compared to lenses of the same formulation placed in apolyvinyl alcohol solution at the same concentration for the sameduration of time but containing a lower molecular weight polyvinylalcohol.

Another example of a contact lens comprises a lens body that comprises areaction product of a polymerizable composition comprising at least onehydrophilic monomer, at least one crosslinking agent, and at least oneophthalmically acceptable acid which can be in a polymerizable form or apolymerized form(s) of an ophthalmically acceptable inorganic acid ororganic acid when added to the polymerizable composition. Ophthalmicallyacceptable inorganic acids can be, for example, a polymerizable orpolymerized form(s) of boronic acid, phosphoric acid, or both.

The present contact lenses can also be provided in a contact lenspackage. A contact lens in accordance with the present disclosure,comprises a contact lens formed from a polymerizable compositioncomprising at least one hydrophilic monomer, at least one crosslinkingagent, and at least one ophthalmically acceptable acid. The contact lenshas a polyol, such as a polyol with at least five hydroxyl groups,present on at least a lens surface of the contact lens body.

Methods of producing a contact lens are also disclosed. An example of amethod of producing a contact lens formed from a polymerizablecomposition comprises preparing a lens body that is the reaction productof a polymerizable composition comprising reactive ingredients. Thereactive ingredients include: at least one hydrophilic monomer, at leastone crosslinking agent, and at least one ophthalmically acceptable acid.The method further comprises the step of contacting the lens body withat least one polyol, such as a 1,3 polyol with at least five hydroxylgroups, from an aqueous solution to attach the polyhydric alcohol to atleast the lens surface.

Methods of using the present contact lenses are also disclosed. As anexample, a method of rewetting the lens surface of a contact lenscomprises contacting the contact lens with at least a second polyol,such as a polyol with at least five hydroxyl groups. The contact lens socontacted has been preformed with a polymerizable composition comprisingat least one hydrophilic monomer, at least one crosslinking agent, andat least one ophthalmically acceptable acid. The preformed lens caninitially have at least one polyol, such as a first polyol with at leastfive hydroxyl groups, present on at least a lens surface of the contactlens body. The rewettable lenses include those formulated with at leastone ophthalmically acceptable acid that can be an organic acid, aninorganic acid, or both. The rewetting treatment permits at least thelens surface of the contact lens to be rewetted or “recharged” after useby a lens wearer, such as by wearing the lens on an eye of the lenswearer, which can further extend the useful life of the lens product.The rewetting can replace lost polyols and/or further add polyols to atleast the surface of the lens to improve wettability and/or otherproperties of the lens.

In another example of the present invention, the ophthalmicallyacceptable acid comprises at least one form of a boronic acid, boronicester, boronic anhydride, or combination thereof. In this example, theat least one form of a boronic acid, boronic ester, boronic anhydride,or combination thereof can be distributed as a second polymer componentin the polymerized reaction product (i.e., within the bulk of the lensbody and at a lens surface thereof), can be present as a polymerizablecomponent of the polymerizable composition, or can be both present as apolymerizable component of the polymerizable composition and distributedas a second polymer component in the reaction product. When the at leastone form of a boronic acid, boronic ester, boronic anhydride, orcombination thereof is a polymerizable form and is present in thepolymerizable composition, after polymerization of the polymerizablecomposition to form the polymerized reaction product comprising acopolymer, the at least one polymerizable form of a boronic acid,boronic ester, boronic anhydride, or combination thereof is present aspolymerized units of the copolymer. In the case where the polymerizablecomposition comprises at least one polymerizable form of a boronic acid,boronic ester, boronic anhydride, or combination thereof; at least onehydrophilic monomer; and at least one crosslinking agent; thepolymerized reaction product comprises polymerized units of the at leastone form of a boronic acid, boronic ester, boronic anhydride, orcombination thereof; polymerized units of the hydrophilic monomer; andcrosslinks formed by the at least one crosslinking agent.

In this example, the lens body that is the polymerized reaction productcan comprise boronic acid moieties present on at least a surface of thelens body or within the bulk of the lens body. In one example, theboronic acid moieties can be present in the copolymer of the lens body.

The lens body comprising boronic acid moieties can have at least onepolyhydric alcohol present on at least one lens surface, i.e., theboronic acid moieties of the lens body can be complexed with 1, 2 diolor 1,3 diol moieties of the polyhydric alcohol such that the polyhydricalcohol is present on at least one lens surface, forming a complexedlens body. The at least one polyhydric alcohol can have at least fivependant hydroxyl groups, as previously described, or can have fewer thanfive hydroxyl groups (i.e., the polyhydric alcohol can have at least twopendant hydroxyl groups). As previously described, the polyhydricalcohol of the present example can comprise a polyhydric alcohol havingat least one 1,3 diol moiety (i.e., a polyhydric alcohol with a backbonecomprising at least three carbon atoms, the at least three carbon atomsbonded in a chain as a right carbon atom bonded to a center carbon atom,the center carbon atom bonded to a left carbon atom, wherein one andonly one hydroxyl group is bonded to the right carbon atom, a hydroxylgroup is not bonded to the center carbon atom, and one and only onehydroxyl group is bonded to the left carbon atom). Additionally, thepolyhydric alcohol of the present example can comprise a polyhydricalcohol having at least one 1, 2 diol moiety, or having both 1, 2 dioland 1,3 diol moieties. The at least one polyhydric alcohol can bepresent on at least one lens surface or can be present on both theanterior lens surface and the posterior lens surface. In some examples,the at least one polyhydric alcohol may be present in the bulk of thelens body as well as on a lens surface. In the example where thepolyhydric alcohol is a polyhydric alcohol having at least one 1, 2 diolor 1,3 diol moiety, at least a portion of 1, 2 diol or 1,3 diol moietiespresent in a solution of the polyhydric alcohol can be complexed with atleast a portion of boronic acid moieties present in the lens body (e.g.,boronic acid moieties present on a lens surface, within the bulk of thelens body, or both). Alternatively, in this example, the boronic acidmoieties present in the lens body may not be complexed with 1, 2 or 1,3moieties of a polyhydric alcohol, i.e., the lens body that is thepolymerized reaction product may be an uncomplexed lens body. In oneparticular example of a method, the uncomplexed lens body can becontacted with a solution of a polyhydric alcohol having 1, 2 diol or1,3 diol moieties, and at least a portion of boronic acid moietiespresent in the lens body can complex with at least a portion of 1, 2diol or 1,3 diol moieties of the polyhydric alcohol present in thesolution, forming a complexed lens body.

The example can comprise a method of manufacturing a hydrogel contactlens body. The method of manufacturing a hydrogel contact lens body cancomprise: (i) providing a lens body comprising at least one form ofboronic acid, boronic ester, boronic anhydride or combination thereof;and (ii) contacting the lens body with a contacting solution comprisingat least one form of tris(hydroxymethyl)aminomethane (TRIS). In oneexample, the at least one form of TRIS can comprise a TRIS buffersystem.

The at least one form of the boronic acid, boronic ester, boronicanhydride or combination thereof can comprise a polymerizable form ofthe at least one form of the boronic acid, boronic ester, boronicanhydride or combination thereof. The at least one polymerizable form ofthe boronic acid, boronic ester, boronic anhydride or combinationthereof can comprise a polymerizable form of boronic acid having thestructure:

The at least one form of boronic acid, boronic ester, boronic anhydrideor combination thereof can be present on at least a surface of the lensbody.

The lens body can comprise a hydrogel lens body. The hydrogel lens bodycan comprise a polymerized reaction product of a polymerizablecomposition, the polymerizable composition comprising at least onehydrophilic monomer and at least one crosslinking agent; and thepolymerized reaction product comprising a polymer formed of polymerizedunits of the at least one hydrophilic monomer, and crosslinks formed bythe at least one crosslinking agent.

When the at least one form of a boronic acid, boronic ester, boronicanhydride, or combination thereof comprises a polymerizable form of aboronic acid, boronic ester, boronic anhydride, or combination thereof,the hydrogel lens body can be a polymerized reaction product of apolymerizable composition, the polymerizable composition comprising theat least one polymerizable form of a boronic acid, boronic ester,boronic anhydride, or combination thereof; at least one hydrophilicmonomer; and at least one crosslinking agent; and the polymerizedreaction product is a copolymer formed of polymerized units of the atleast one polymerizable form of the boronic acid, boronic ester, boronicanhydride or combination thereof, polymerized units of the at least onehydrophilic monomer, and crosslinks formed by the at least onecrosslinking agent.

The lens body (e.g., a complexed lens body or an uncomplexed lens body)can have an advancing contact angle less than about 120°, a modulus lessthan about 1.6 MPa, an ionoflux less than about 7×10⁻³ mm²/min., anoxygen permeability of less than about 120 Barrers, and an equilibriumwater content of at least about 30%.

In another example, the lens body (e.g., an uncomplexed lens body or acomplexed lens body) can have an advancing contact angle less than about100°, a modulus from about 0.3 MPa to about 1.0 MPa, an ionoflux lessthan about 5×10⁻³ mm²/min., an oxygen permeability of less than about110 Barrers, and an equilibrium water content from about 35% to 65%.

In yet another example, the lens body (e.g., a complexed lens body or anuncomplexed lens body) can have an advancing contact angle less thanabout 60°, a modulus from about 0.4 MPa to about 0.7 MPa, an ionofluxless than about 4×10⁻³ mm²/min., an oxygen permeability from about 55Barrers to about 100 Barrers, and an equilibrium water content fromabout 40% to 65%.

The at least one form of TRIS comprises a form oftris(hydroxymethyl)aminomethane in combination with at least one form ofethylenediaminetetraacetic acid (EDTA). The at least one form oftris(hydroxymethyl)aminomethane in combination with at least one form ofethylenediaminetetraacetic acid (EDTA) can comprise a (TRIS-EDTA) buffersystem. The form of EDTA can comprise ethylenediaminetetraacetic acidsodium salt dihydrate. The TRIS-EDTA buffer system can further comprisetris(hydroxymethyl)aminomethane hydrochloride (TRIS HCl). The form ofEDTA can comprise ethylenediaminetetraacetic acid sodium salt dihydrate.

The contacting solution can further comprise a tonicity adjusting agent.The contacting solution can have an osmolarity from about 100 mOsm toabout 300 mOsm.

The contacting solution further can further comprise at least onesurfactant. The contacting solution can further comprise at least onewetting agent or comfort agent.

The contacting solution can further comprise at least one polyhydricalcohol having at least one 1,2 diol or 1,3 diol moiety, wherein atleast a portion of the 1, 2 diol or 1,3 diol moieties present in thesolution are capable of complexing with at least a portion of boronicacid moieties present in the lens body.

The step of contacting the lens body with the contacting solution cancomprise soaking the lens body in the contacting solution, rinsing thelens body with the contacting solution, or both soaking and rinsing thelens body.

The step of contacting the lens body with the contacting solution cancomprise placing the lens body in a contact lens package with thesolution, sealing the package, and sterilizing the package. When thecontacting solution comprises a form of poly(vinyl alcohol) (PVOH), theat least one form of TRIS can be present in the solution at aconcentration effective to prevent gelation of the form of PVOH over ashelf life of the sterilized package.

The example can also comprise a method of treating a hydrogel contactlens. The method of treating a hydrogel contact lens can comprise: (i)providing a contact lens comprising at least one form of boronic acid,boronic ester, boronic anhydride or combination thereof; (ii) prior tothe contact lens being worn by a user, contacting the lens body with afirst contacting solution comprising at least one form oftris(hydroxymethyl)aminomethane (TRIS); and (iii) subsequently to thecontact lens being worn by the user, contacting the lens body with asecond contacting solution comprising at least one form of TRIS. The atleast one form of TRIS of the first contacting solution can be the sameas the at least one form of TRIS of the second contacting solution, orcan be different.

The example can also be directed to a hydrogel contact lens product. Thehydrogel contact lens product can comprise: (i) a lens body comprisingat least one form of boronic acid, boronic ester, boronic anhydride orcombination thereof; (ii) a packaging solution comprising at least oneform of tris(hydroxymethyl)aminomethane (TRIS); (iii) a contact lenspackage base member with a cavity configured to hold the lens body andthe packaging solution; and (iv) a seal attached to the base memberconfigured to maintain the lens body and the packaging solution in asterile condition for a duration of time equivalent to a shelf life ofthe contact lens package.

The at least one form of TRIS can be present in the packaging solutionat a concentration effective to lower an effective pKa of boronic acidmoieties present on at least a surface of the lens body. The packagingsolution can further comprise at least one polyhydric alcohol having atleast one 1,2 diol or 1,3 diol moiety, and at least a portion of boronicacid moieties present on at least a surface of the lens body can becomplexed with at least a portion of 1,2 diol or 1,3 diol moietiespresent in the solution of at least one polyhydric alcohol. The at leastone form of TRIS can be present in the packaging solution at aconcentration effective to prevent gelation of the packaging solutionover a shelf life of the sterilized package.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are intended to provide a further explanation of the presentinvention, as claimed.

The accompanying figures, which are incorporated in and constitute apart of this application, illustrate various embodiments of the presentinvention and, together with the description, serve to explainprinciples of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a series of 4 schematic drawings (FIG. 1A, FIG. 1B, FIG. 1C,and FIG. 1D) illustrating polymerization reactions that result in theformation of a polymer of an ophthalmically acceptable acid (i.e.,4-vinylphenyl boronic acid (VPB)), and the attachment of a polyol (i.e.,a 1,3 polyvinyl alcohol having five or more hydroxyl groups attached) tothe polymer of the acid.

FIG. 2 is a graph demonstrating the accumulated uptake of polyvinylalcohol over time of hydrogel contact lens products manufactured with anopthalmically acceptable acid and a control lens manufactured withoutthe acid.

FIG. 3 is a graph demonstrating the lens uptake and release of polyvinylalcohol over time of hydrogel contact lens products manufactured with anophthalmically acceptable acid and a control lens manufactured withoutthe acid.

FIG. 4 is a graph demonstrating the rate of uptake of a first form ofpolyvinyl alcohol by lenses made from a series of hydrophobicformulations containing 0 unit parts to 3 unit parts of theophthalmically acceptable acid.

FIG. 5 is a graph demonstrating the rate of uptake of a second form ofpolyvinyl alcohol by lenses made from a series of hydrophobicformulations containing 0 unit parts to 3 unit parts of theophthalmically acceptable acid.

FIG. 6 is a graph demonstrating the rate of uptake of the first form ofpolyvinyl alcohol by lenses made from a series of hydrophilicformulations containing 0 unit parts to 3 unit parts of theophthalmically acceptable acid.

FIG. 7 is a graph demonstrating the rate of uptake of the second form ofpolyvinyl alcohol by lenses made from a series of hydrophilicformulations containing 0 unit parts to 3 unit parts of theophthalmically acceptable acid.

DETAILED DESCRIPTION

New contact lenses are disclosed. The contact lenses can comprise atleast one ophthalmically acceptable acid. The contact lenses optionallycan have a wetting agent or component present on at least the surface ofthe contact lens or portion thereof. The wetting agent or wettingcomponent can be present on at least the surface of the contact lens orportion thereof by associating with at least a portion of the lens body,such as by grafting, chemical bonding, covalent bonding, or other formsof chemical attachment or physical attachment or both. The wetting agentthat attaches onto the surface of the contact lens retains wettability,for instance, based on in vitro tests or other tests, over an extendedperiod of time, for instance, at least 6 hours, at least 12 hours, atleast 24 hours, at least 48 hours (such as from about 12 hours to 72hours or more). The wetting agent can, for instance, be a hydroxyl- orhydroxy-containing wetting agent. The wetting agent has the ability toattach, such as by chemical attachment, onto at least the surface of thecontact lens, such as by way of or through one or more wetting agentlinkers, such as an ophthalmically acceptable acid or radical thereof ormoiety thereof. As shown, for instance, in FIGS. 1A, 1B, 1C and 1D,which are purely exemplary, a polymerizable form of acid can react toform a polymerized form of the acid present in a lens body. The lensbody comprising the polymerized acid can then be contacted with awetting agent, such as a polyol, such as a polyol with at least fivehydroxyl groups, and including forms of polyvinyl alcohol. Without beingbound by any particular theory or mechanism of action, it is believedthat contacting the lens body with the wetting agent results in thewetting agent attaching to at least a surface of the lens body, makingthe lens body wettable. It is possible that the wetting agent attachesonto at least the lens surface through a chemical bond with at least aportion of the wetting agent linker, such as an ophthalmicallyacceptable acid or radical thereof or moiety thereof that is presentwithin the lens including on the surface of the lens.

Further, the present contact lenses include at least one lens surfacethat can be re-wetted or re-charged by exposing the contact lens to awetting agent, which can be the same or different from the originalwetting agent to replace at least a portion of any previously attachedwetting agent that may have been lost through use or other reasonsand/or to add additional wetting agent onto the lens surface. One ormore (such as two or more, three or more, four or more, and the like)ophthalmically acceptable acids can be present in the lens as part ofthe lens composition. Further, one or more wetting agents can beattached to the lens surface, such as two or more, three or more, fouror more, and the like.

In accordance with the present disclosure, a contact lens comprises apolymerized composition, wherein the polymerized composition includes atleast one ophthalmically acceptable acid or units of at least oneophthalmically acceptable acid. The contact lens optionally can furthercomprise at least one wetting agent (which includes the wetting agent ormoiety thereof or radical thereof) attached to at least a portion of thepolymerized composition. The wetting agent can be at least one polyoland the wetting agent can be attached to at least a portion of theavailable ophthalmically acceptable acid or radical thereof or moietythereof. The ophthalmically acceptable acid, or at least a substantialpart of it, remains present in the polymerized composition and is notsubstantially extracted or washed out during lens processing or wear.

The wetting agent linker, such as the ophthalmically acceptable acid,can be present throughout the entire lens composition and can be part ofthe lens composition. As an option, the concentration of the wettingagent linker can be different at the surface compared to non-surfaceportions of the lens body. Various gradients of concentrations of thewetting agent linker can be present throughout the lens composition,such that the concentration of the wetting agent linker is uniformthroughout the lens or is non-uniform throughout the lens. Theconcentration of the wetting agent linker can be substantially uniformthroughout the lens and this can be achieved by adding the wetting agentlinker, such as the ophthalmically acceptable acid, in the compositionforming the lens and distributing the wetting agent linker uniformlythroughout the composition prior to formation of the lens. As an option,the wetting agent linker can be added after a certain time after the oneor more of the other reactive components forming the lens compositionare added or once polymerization begins in order to have the wettingagent linker more concentrated at one or more locations in the lenscomposition such as, for example, at a lens surface.

In some examples, as an option, the wetting agent linker is not presentonly as a coating or layer on the lens surface, but is an integral partof the overall lens composition and, thus, the lens that is formed fromthe lens composition. While it is optional to include an additionallayer on the lens surface that can also contain a wetting agent linker,it is to be understood that this is not necessary and, in fact, byhaving a wetting agent linker incorporated as part of the overall lenscomposition and part of the overall lens, there is no need to have aseparate coating or layer of acid or other wetting linker to enhance theability to be wetted. Further, when using a coating or layer alone, thiscoating or layer is subjected to being worn and removed and, thus, willneed to be replaced whereas, in the present contact lenses, by having awetting agent linker incorporated within and part of the overall lenscomposition and, thus, the lens, there is no concern with having thislinker removed or worn off.

Further, as an option, the wetting agent linker, such as theophthalmically acceptable acid, is not present alone as a post-treatmentafter formation of the lens body. In other words, with the presentcontact lenses, the wetting agent linker is not present due to apost-treatment on the lens body already formed. As stated, the wettingagent linker, such as the ophthalmically acceptable acid, is part of thelens body and remains part of the lens body. For example, the wettingagent linker can be provided as an ingredient of the polymerizablecomposition that is polymerized to form a contact lens.

Further, as an option, the wetting agent linker, such as theophthalmically acceptable acid, or at least a major portion thereof, isnot extractable with alcohol or chloroform and this means that less than10 wt %, or less than 5 wt %, or less than 1 wt %, or less than 0.5 wt%, or less than 0.1 wt % of the wetting agent linker, such as theophthalmically acceptable acid, is capable of being removed byextraction. For example, in certain embodiments, only 0.001 wt % to 0.3wt % of the wetting agent linker that is present in the lens at the timeof formation is removed over time by extraction.

As stated, the wetting agent linker, such as the ophthalmicallyacceptable acid, is part of or within the unitary construction of thelens body. In one example, the acid is present as a polymerized productof the lens composition forming the lens body.

In certain embodiments of the present contact lenses, a contact lens isassociated with a time release of an attached wetting agent from atleast the lens surface. The time release can be for at least 6 hours, atleast 12 hours, for at least 24 hours, for at least 48 hours, or more.The time release of the wetting agent can be constant over the timerelease period or it can be front-loaded where a larger percentage isreleased initially over time. For a constant rate of release, therelease profile will appear to be substantially linear for the durationof the measurement period. In embodiments in which the wetting agent isreleased in greater amounts over a shorter period of time, the releaseprofile may be characterized as having a relatively steep first profileportion and a relatively shallow second profile portion or a plateauportion. Some embodiments of the present lenses may have releaseprofiles that are sigmoidal in shape, that is, characterized by arelatively slow rate of release, followed by a faster rate of release,and subsequently followed by a relatively slower rate of release. Thus,the release profiles may also be monophasic, biphasic, or triphasic.

Another aspect of the present contact lenses relates to a non-leachingacid containing contact lens where the ophthalmically acceptable acid ispart of the lens composition forming the lens and the non-leachingproperty is with respect to not being able to leach a substantial amountof the acid from the lens with alcohol or an aqueous solution over aperiod of at least 6 hours in the alcohol or aqueous solution and havingthe low acid extractable content described herein. In one example, theophthalmically acceptable acid can be a polymerizable form of theophthalmically acceptable acid. When included as part of the compositionforming the lens, the polymerizable form of the ophthalmic acid canpolymerize as part of the lens body, and so can be essentially orentirely bound within the polymerized lens body and can be removed onlyby breaking the polymer bonds formed during the curing of the lens.

In one example, the wetting agent linker, such as the ophthalmicallyacceptable acid, is part of the composition forming the lens, such asthe polymerized composition forming the lens, and can be present withone or more conventional components found in a contact lens, such as ahydrogel contact lens including, but not limited to, at least onepolymer (such as at least one hydrophilic polymer, at least onehydrophobic polymer, or combinations thereof); optionally at least onecrosslinking agent; optionally at least one initiator; optionally, atleast one tinting agent; optionally at least one UV blocking agent,wherein the polymer present in the polymerized composition can be ahomopolymer, copolymer, interpenetrating polymer network (IPN), blockpolymer, and/or other forms of polymer. It is to be understood thatreference to the polymerized composition, which is formed from the atleast one polymer, is a polymer which can be formed from one or moremonomers, such as one or more hydrophilic monomers, one or morehydrophobic monomers, combinations thereof, and the like. It is also tobe understood that reference to the contact lens formed from thecompositions described herein is a lens body with an anterior surfaceand a posterior surface, the posterior surface being configured to beplaced in contact with the cornea of an eye of a contact lens wearer.The lens body of the present invention can be entirely transparent.Alternatively, when the contact lens is a cosmetic lens configured toalter the appearance of an iris of a contact lens wearer, the lens bodycan comprise a transparent optic zone circumscribed by a cosmeticportion dimensioned to overlay the iris of the eye. Transparent lensesmay also include a handling tint to provide a color to the lens.

As an example, contact lenses having extended and rechargeablewettability comprise a lens body that comprises a reaction product of apolymerizable composition including at least one ophthalmicallyacceptable acid, which is at least surface treated with a first 1,3polyol with at least five pendant hydroxyl groups to attach the polyolto the lens, including at least the surface. The ophthalmicallyacceptable acid is distributed in the reaction product within the lensbody including some exposure at a lens surface thereof. Theophthalmically acceptable acid of the lens body, having an anteriorsurface and a posterior surface, interacts with the polyol with at leastfive pendant hydroxyl groups to attach the polyol to at least the lenssurface. The resulting lens body with the treated lens surface has goodwettability, such as can be shown by an advancing contact angle of lessthan 100° and/or a water break up time (WBUT) of greater than fiveseconds, which are maintained following in vitro testing for a durationof at least 6 hours. The present contact lenses when worn can be incontact with epithelial tissue or other eye tissues. The present contactlenses can be soft contact lenses, hard contact lenses, or hybridcontact lenses comprising a rigid central portion circumscribed by asoft peripheral portion. As used herein, a soft contact lens is acontact lens that can conform to the shape of the cornea of an eye of alens wearer or can otherwise be folded upon itself without breaking. Ahard contact lens is a contact lens that cannot be folded upon itselfwithout breaking. A soft contact lens can be a hydrogel contact lens,that is, a contact lens that is capable of retaining water in anequilibrium state. The hydrogel contact lens can be a silicone-freehydrogel contact lens or a silicone hydrogel contact lens. Otherfeatures and examples of the present contact lenses are described in thefollowing sections.

In an example of the present contact lenses, the contact lens is a lenshaving at least one optic zone configured to provide vision correction,to improve visual acuity, or to both provide vision correction andimprove visual acuity. For example, the optic zone can be configured toprovide a spherical correction, a toric correction, or a third order orhigher correction. The optic zone can be configured to improve visualacuity at near viewing distances, at far viewing distances, or at bothnear and far viewing distances. The present contact lenses can bespherical contact lenses, such as for correcting myopia or hyperopia;toric contact lenses, such as for correcting astigmatism; multifocalcontact lenses, such as bifocal contact lenses, trifocal contact lenses,and the like for providing more than one refractive power.

The ophthalmically acceptable acid present in the composition or in thecontact lens can be neutralized (e.g, partially or to various degrees),as an option. The pH of the overall composition containing theophthalmically acceptable acid can be controlled or adjusted to achievean optimal binding pH for the polyhydric alcohol, and this can be aboveor the same as or below a pKa of the acid species present.

As an option, the lens body which contains the ophthalmically acceptableacid can be first treated and/or recharged at elevated temperatures,such as 50 to 80 degrees C. or higher which can favorably reduce theamount of time to treat and/or recharge the lens body and thus place thewetting agent faster and/or more effectively on the lens surfaces.

Wetting drops containing a polyhydric alcohol or the same polyhydricalcohol can be used to recharge at least a portion of the lens. Thewetting drops can be introduced to the lens when the lens is on the eyeor when not in the eye. This is especially useful for the recharge ofthe anterior surface of the lens.

Definitions. In the context of the present description and claims, thefollowing terminology will be used in accordance with the definitionsdescribed below.

As used herein, the term “hydrogel” refers to a polymeric material,typically a network or matrix of polymer chains, capable of swelling inwater or becoming swollen with water. A hydrogel can also be understoodto be a material that retains water in an equilibrium state. The networkor matrix may or may not be cross-linked. Hydrogels refer to polymericmaterials, including contact lenses that are water swellable or arewater swelled. Thus, a hydrogel may be (i) unhydrated and waterswellable, or (ii) partially hydrated and swollen with water, or (iii)fully hydrated and swollen with water. The hydrogel may be a siliconehydrogel, a silicone-free hydrogel, or an essentially silicone-freehydrogel.

The term “silicone hydrogel” or “silicone hydrogel material” refers to aparticular hydrogel that includes a silicon (Si)-containing component ora silicone-containing component. For example, a silicone hydrogel istypically prepared by combining a silicon-containing material withconventional hydrophilic hydrogel precursors. A silicone hydrogelcontact lens is a contact lens, including a vision correcting contactlens, which comprises a silicone hydrogel material.

A “silicone-containing component” is a component that contains at leastone [—Si—O—Si—] linkage, in a monomer, macromer or pre-polymer, whereineach silicon atom may optionally possess one or more organic radicalsubstituents (R₁, R₂) or substituted organic radical substituents thatmay be the same or different, e.g., —SiR₁R₂O—.

An “essentially silicone-free hydrogel” refers to a hydrogel containingless than 0.1% (w/w) silicone-containing component.

The term “linker” is used herein to refer to an atom or a collection ofatoms used to link interconnecting moieties, such as a polymer terminusand a block of repeat units. A linker moiety may be hydrolyticallystable or may include a physiologically hydrolyzable or enzymaticallydegradable linkage. The linkers can be hydrolytically stable.

The term “length”, e.g., in reference to a collection of atoms such asin a linker having a particular atom length, e.g., ranging from 2 to 50atoms in length, is based upon the number of atoms in the longest chainof the collection of atoms, regardless of substituents. For example,—CH₂CH₂— is considered as having a length of two carbon atoms, eventhough each methylene group itself contains three atoms total, since thehydrogen atoms are substituents on the carbon and are not considered inapproximating overall length of the chain. The linker,—O—C(O)—CH₂CH₂C(O)NH—, is similarly considered to possess a chain lengthof six atoms.

“Polyvinyl alcohols” or “poly(vinyl alcohols)” (abbreviated “PVOH”) isthe name for polymers comprising the general structure[—CH₂—CH(OH)—]_(m), where m is a value of 1 or greater. The term“polyvinyl alcohol” also can refer to PVOH as a functional groupattached to another molecular structure with one or more pendanthydroxyl groups of the PVOH intact.

“Attach” in the context of an interaction of PVOH and the ophthalmicallyacceptable acid can refer to any of graft, complex, bond (chemical bondor hydrogen), or adhere, unless specified otherwise. The PVOH attachmentalso can be “semi-permanent,” such as optionally allowing for slowrelease of the attached PVOH from the acid during use, which may enhancecomfort during lens wear.

“Molecular mass” in the context of a polymer described herein refers tothe nominal average molecular mass of a polymer, typically determined bysize exclusion chromatography, light scattering techniques, or intrinsicvelocity determination in 1,2,4-trichlorobenzene. Molecular weight inthe context of a polymer can be expressed as either a number-averagemolecular weight or a weight-average molecular weight, and in the caseof vendor-supplied materials, will depend upon the supplier. Typically,the basis of any such molecular weight determinations can be readilyprovided by the supplier if not provided in the packaging material.Typically, references herein to molecular weights of macromer orpolymers herein refer to the weight average molecular weight. Bothmolecular weight determinations, number-average and weight-average, canbe measured using gel permeation chromatographic or other liquidchromatographic techniques. Other methods for measuring molecular weightvalues can also be used, such as the use of end-group analysis or themeasurement of colligative properties (e.g., freezing-point depression,boiling-point elevation, or osmotic pressure) to determinenumber-average molecular weight or the use of light scatteringtechniques, ultracentrifugation or viscometry to determineweight-average molecular weight.

A “network” or “matrix” of a hydrophilic polymer typically means thatcrosslinks are formed between the polymer chains by covalent bonds or byphysical bonds, e.g. hydrogen bonds. A network can include two or morepolymeric components, and can include an interpenetrating polymernetwork (IPN) in which one polymer is physically entangled with a secondpolymer such that there are few, if any, covalent bonds between them,but the polymers cannot be separated from each other without destroyingthe network.

A “hydrophilic” substance is one that is water-loving or has an affinityfor water. Hydrophilic compounds have an affinity to water and areusually charged or have polar moieties or groups that attract water.

A “hydrophilic polymer” as used herein is defined as a polymer having anaffinity for water and capable of absorbing water. A hydrophilic polymeris not necessarily soluble in water.

A “hydrophilic component” is a hydrophilic substance that may or may notbe a polymer. Hydrophilic components include those that are capable ofproviding at least from about 20% (w/w), for example, at least fromabout 25% (w/w) water content to the resulting hydrated lens whencombined with the remaining reactive components. A hydrophilic componentcan include hydrophilic monomers, hydrophilic macromers, hydrophilicpre-polymers, hydrophilic polymers, or combinations thereof. Hydrophilicmacromers, hydrophilic pre-polymers, and hydrophilic polymers may alsobe understood to have hydrophilic portions and hydrophobic portions.Typically, the hydrophilic portion and the hydrophobic portion will bepresent in relative amounts such that the macromers, pre-polymers, orpolymers are hydrophilic.

A “monomer” refers to a relatively low molecular weight compound, forexample a compound with an average molecular weight less than about 700Daltons, that is polymerizable. In one example, a monomer can comprise asingle unit of a molecule containing one or more functional groupscapable of polymerizing to combine with other molecules to form apolymer, the other molecules being of the same structure or differentstructures as the monomer.

A “macromer” refers to medium and high molecular weight compounds orpolymers, which can contain one or more functional groups capable offurther polymerization. For example, a macromer can be a compound withan average molecular weight of between about 700 Daltons and about 2,000Daltons.

A “pre-polymer” refers to a polymerizable or crosslinkable highermolecular weight compound. In one example, a pre-polymer can be a seriesof monomers or macromers bonded together such that the overall moleculeremains polymerizable or crosslinkable. For example, a pre-polymer canbe a compound with an average molecular weight greater than about 2,000Daltons.

A “polymer” refers to a material formed by polymerizing one or moremonomers, macromers or pre-polymers. As used herein, a polymer isunderstood to refer to a molecule that is not capable of beingpolymerized, but is capable of being crosslinked to other polymers, forexample, to other polymers present in a polymerizable composition orduring the reaction of monomers, macromers or pre-polymers to form otherpolymers in a polymerizable composition.

An “interpenetrating polymer network” or “IPN” refers to a combinationof two or more different polymers, in network form, of which at leastone is synthesized and/or cross-linked in the presence of the otherwithout any covalent bonds between them. An IPN can be composed of twokinds of chains forming two separate networks, but in juxtaposition orinterpenetrating. Examples of IPNs include sequential IPNs, simultaneousIPNs, semi-IPNs and homo-IPNs.

A “pseudo IPN” refers to a polymeric reaction product where at least oneof the different polymers is cross-linked while at least one otherpolymer is non-crosslinked (e.g. linear or branched), wherein thenon-cross-linked polymer is distributed in and held by the cross-linkedpolymer on a molecular scale such that the non-cross-linked polymer issubstantially inextractable from the network.

A “polymeric mixture” refers to a polymeric reaction product whereindifferent polymers are both linear or branched, substantially withoutcross-linking, wherein the resulting polymeric blend that is obtained isa polymer mixture on a molecular scale.

A “graft polymer” refers to a branched polymer haying side chainscomprising a homopolymer or copolymer different to that of the mainchain.

“Attach” can refer to any of charge attachment, graft, complex, bond(chemical bond or hydrogen), or adhere, unless specified otherwise.

As used herein, an “ophthalmically acceptable lens forming component”refers to a lens forming component that can be incorporated into ahydrogel contact lens without the lens wearer experiencing or reportingsubstantial discomfort, including ocular irritation and the like.Ophthalmically acceptable hydrogel contact lenses have ophthalmicallyacceptable surface wettabilities, and typically do not cause or are notassociated with significant corneal swelling, corneal dehydration (“dryeye”), superior-epithelial arcuate lesions (“SEALs”), or othersignificant discomfort.

Additional definitions may also be found in the sections that follow.

Lens formulations. Hydrogels represent one class of materials used forthe present contact lenses. Hydrogels comprise a hydrated, cross-linkedpolymeric system containing water in an equilibrium state. Accordingly,hydrogels are copolymers prepared from one or more hydrophilic monomers.The hydrophilic monomers are crosslinkable with a crosslinking agent.

The contact lenses can generally relate to hydrogel contact lensinclusive of silicone hydrogel and silicone-free (or essentiallysilicone-free) hydrogel lens materials. The hydrogel contact lenses havesome features in common for purposes of the present invention. Thesefeatures include, for example, a lens body of the contact lens thatcomprises a reaction product of a polymerizable composition comprisingat least one hydrophilic monomer, at least one crosslinking agent thatcrosslinks the hydrophilic monomer during polymerization to form a firstpolymer component, and at least one ophthalmically acceptable acid. Theophthalmically acceptable acid can be distributed as a polymer componentin polymeric or macromeric form in the reaction product within the lensbody and at a lens surface thereof. Further, the lens body of thepolymerized composition further is at least provided with at least onepolyol, for example a 1, 3 polyol with at least five pendant hydroxylgroups. The polyol is attached to or present on at least a lens surfaceof the lens body via the ophthalmically acceptable acid.

Hydrophilic monomer. The hydrophilic monomer can be, for example, asilicone-containing monomer having a hydrophilic portion, a hydrophilicsilicone-free monomer, or a combination thereof, which is compatiblewith the ophthalmically acceptable acid. The hydrophilic monomer can beused in combination with a hydrophobic monomer. The hydrophilic monomercan be a monomer having both hydrophilic and hydrophobic portions ormoieties. The type and amount of hydrophilic monomer used in thepolymerizable lens composition can vary depending on the types of otherlens-forming monomers that are used. Non-limiting illustrations areprovided herein with respect to hydrophilic monomers for use in siliconehydrogels and silicone-free hydrogels.

Crosslinking Agent. Crosslinking agents for the monomers, macromers orboth, used in preparing the hydrogels can include those that are knownin the art, and examples of the crosslinking agents are also providedherein. Suitable crosslinking agents include, for example, a diacrylate-(or divinyl ether-) functionalized ethylene oxide oligomer or monomer,such as, for example, tri(ethylene glycol)dimethacrylate (TEGDMA),tri(ethylene glycol)divinyl ether (TEGDVE), ethylene glycoldimethacrylate (EGDMA), and trimethylene glycol dimethacrylate (TMGDMA).Typically, the crosslinking agents are present in the polymerizablesilicone hydrogel composition in relatively small total amounts in thepolymerizable composition, such as in an amount ranging from about 0.1%(w/w) to about 10% (w/w), or from about 0.5% (w/w) to about 5% (w/w), orfrom about 0.75% (w/w) to about 1.5% (w/w), by weight of thepolymerizable composition.

Ophthalmically acceptable acid. As previously stated, the ophthalmicallyacceptable acid is an acid capable of being immobilized chemically,physically, or both chemically and physically, in the lens body,including at least at a wetting portion at a surface of the lens body.The acid (or at least a portion, or significant portion) present in thepolymerized lens body is not extracted or washed out during typicalmanufacturing, storage, and/or wear conditions (e.g., at least 90% byweight of the acid present when the lens is formed remains afterwards,such as from 90 wt % to 100 wt %, 95 wt % to 99.99 wt %, 97 wt % to 99wt %, or 98 wt % to 99 wt %).

In one example, the ophathamically acceptable acid is a polymerizableacid, including a monomer, a macromer, or a pre-polymer comprising anophthalmically acceptable acid moiety, as well as at least onefunctional group capable of polymerizing to combine with other moleculesunder the conditions used to prepare a polymerized contact lens body. Inanother example, the ophthalmically acceptable acid is a polymer capableof crosslinking with other components in the polymerizable compositionduring polymerization of the polymerizable composition to form thereaction product. The component of the polymerizable composition sourcedfrom the ophthalmically acceptable acid can be a preformed polymer, apre-polymer, a macromer or a monomer introduced to the polymerizablemixture forming the reaction product (e.g., the lens body), which can bedistributed within the reaction product following polymerization. Inanother example, the ophthalmically acceptable acid can be distributedin the reaction product as a polymer, pre-polymer, macromer or monomerof an ophthalmically acceptable acid that is physically immobilized byanother polymer component of the reaction product. The physicalimmobilization of the polymer, pre-polymer, macromer or monomer of theophthalmically acceptable acid can be as an IPN, pseudo-IPN, orpolymeric mixture, or any combination thereof. The component of thepolymerizable composition sourced from the ophthalmically acceptableacid can be formed in situ in the formation of the reaction product ofthe lens body. The ophthalmically acceptable acid can, for example,co-polymerize with or graft onto another polymerizable component in thepolymerizable composition.

The ophthalmically acceptable acid can be a polymerizable form of anophthalmically acceptable inorganic acid or an ophthalmically acceptableorganic acid. The ophthalmically acceptable inorganic acid can be, forexample, a form of boronic acid or phosphoric acid, inclusive ofpolymerizable and polymerized forms thereof. Boronic acids can be, forexample, vinylphenyl boronic acids and derivatives thereof. Vinylphenylboronic acids can be, for example, 2-vinylphenyl boronic acid,3-vinylphenyl boronic acid, 4-vinylphenyl boronic acid, 4-vinylphenylboronic acid MIDA ester, (meth)acrylamido phenyl boronic acid,2-(methacrylamido)phenyl boronic acid pinacol ester,3-acrylamidophenylboronic acid, separately and in combinations thereof.The vinylphenyl boronic acid can, for example, have the followingstructure (1):

Other boronic acids that may be used include those described, forexample, in U.S. Patent Application Publication Nos. 2007/0030443 A1,2007/0116740 A1 and 2008/0151180 A1, which are incorporated herein byreference in their entireties.

The ophthalmically acceptable organic acid can be, for example,1-hydroxy-2-naphthoic acid, 2,2-dichloroacetic acid,2-hydroxyethanesulfonic acid, 2-oxoglutaric acid, 4-acetamidobenzoicacid, 4-aminosalicylic acid, acetic acid, adipic acid, ascorbic acid(L), aspartic acid (L), benzenesulfonic acid, benzoic acid, camphoricacid (+), camphor-10-sulfonic acid (+), capric acid (decanoic acid),caproic acid (hexanoic acid), caprylic acid (octanoic acid), carbonicacid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfiiric acid,ethane-1,2-disulfonic acid, ethanesulfonic acid, formic acid, fumaricacid, galactaric acid, gentisic acid, glucoheptonic acid (D), gluconicacid (D), glucuronic acid (D), glutamic acid, glutaric acid,glycerophosphoric acid, glycolic acid, hippuric acid, hydrobromic acid,hydrochloric acid, isobutyric acid, lactic acid (DL), lactobionic acid,lauric acid, maleic acid malic acid (−L), malonic acid, mandelic acid(DL), methanesulfonic acid, naphthalene-1,5-disulfonic acid,naphthalene-2-sulfonic acid, nicotinic acid, nitric acid, oleic acid,oxalic acid, palmitic acid, pamoic acid, proprionic acid, pyroglutamicacid (−L), salicylic acid, sebacic acid, stearic acid, succinic acid,sulfuric acid, tartaric acid (+L), thiocyanic acid, toluenesulfonic acid(p), undecylenic acid, a polymerizable form of one of the above acids,and any combinations thereof.

In an example where the ophthalmically acceptable acid is VPB and thepolyhydric alcohol is PVOH, a relatively small amount of VPB, forexample, can be used in the polymerizable lens composition in order toproduce a lens surface to attach sufficient PVOH or other polyhydricalcohol to achieve a wettable surface. The ophthalmically acceptableacid can be used, for example, in the polymerizable lens composition, aswell as on the lens surface, in amounts of from about 0.01% (w/w) toabout 10% (w/w), or from about 0.05% to about 5% (w/w), or from about0.1% (w/w) to about 0.5% (w/w), or from about 0.1% (w/w) to about 0.3%(w/w), or other amounts, based on the total lens formulation weight.

Polyhydric Alcohol. The polyhydric alcohol provided on at least thesurface of the lens body can be, a polyhydric alcohol with a backbonecomprising at least three carbon atoms, the at least three carbon atomsbonded in a chain as a right carbon atom bonded to a center carbon atom,the center carbon atom bonded to a left carbon atom, wherein one andonly one hydroxyl group is bonded to the right carbon atom, a hydroxylgroup is not bonded to the center carbon atom, and one and only onehydroxyl group is bonded to the left carbon atom. For example, when thepolyhydric alcohol is a diol, it is not a diol wherein the two hydroxylgroups are on the same carbon atom (i.e., the diol is not a geminaldiol, such as, for example, a 1,1 diol). In another example, thepolyhydric alcohol is not a diol wherein the two hydroxyl groups areattached to adjacent carbon atoms (i.e., the diol is not a vicinal diol,such as, for example, a 1, 2 diol). In another example, the firstpolyhydric alcohol comprises a diol wherein the two hydroxyl groups arepositioned on a backbone of at least 3 carbon atoms, three of the atleast 3 carbon atoms being a chain of 3 carbon atoms comprising a rightcarbon atom bonded to a center carbon atom and the center carbon atombonded to a left carbon atom, such that one hydroxyl group is bonded tothe right carbon, the center carbon atom does not have a hydroxyl groupbonded to it, and the second hydroxyl group is bonded to the left carbonin the chain (i.e., the diol is a 1,3 diol).

In another example, the first polyhydric alcohol can comprise a polyolwith a backbone of more than 3 atoms with more than two pendant hydroxylgroups bonded to the backbone, wherein three carbon atoms of thebackbone comprise a chain of 3 carbon atoms comprising a right carbonatom bonded to a center carbon atom and the center carbon atom bonded toa left carbon atom, wherein additional atoms can be present in thebackbone before or after the chain of 3 carbon atoms, and wherein thechain of 3 carbon atoms only has 2 of the more than 2 pendant hydroxylgroups bonded to the 3 carbons such that one and only one of thehydroxyl groups is bonded to the right carbon atom, no hydroxyl groupsare bonded to the center carbon atom, and the second one and only one ofthe hydroxyl groups is bonded to the left carbon atom. For example, thepolyhydric alcohol can be a 1,3 polyol, a 2,4 polyol, a 3,5 polyol, etc.In another example, the first polyhydric alcohol comprises a polyol withat least 5 pendant hydroxyl groups, such as, for example, a 1,3 polyolwith at least 5 pendant hydroxyl groups, a 2,4 polyol with at least 5pendant hydroxyl groups, a 3,5 polyol with at least 5 pendant hydroxylgroups, etc. In another example, the first polyhydric alcohol comprisesa 1,3 polyol with at least 5 pendant hydroxyl groups, wherein the polyolhas a backbone of more than 3 carbon atoms, one and only one of thehydroxyl groups is bonded to the 1^(st) carbon in the chain, no hydroxylgroups are bonded to the second carbon atom in the chain, another oneand only one of the hydroxyl groups is bonded to the 3^(rd) carbon atomin the chain, and the remaining at least two hydroxyl groups are bondedto atoms of the backbone after the 4^(th) carbon of the backbone (e.g.,the 5^(th), 6^(th), 7^(th) atoms of the backbone, etc.) In yet anotherexample, the first polyhydric alcohol comprises a polyol with a backboneof more than 3 carbon atoms bonded to at least five pendant hydroxylgroups, wherein at least two hydroxyl groups are positioned on the chainof more than 3 carbon atoms such that there is a repeating series of aright carbon atom without a hydroxyl group bonded to a left carbon atomwith one and only one hydroxyl group. Examples of this type ofpolyhydric alcohol include 1,3,5 polyols, 2,4,6 polyols, etc.

The polyhydric alcohol provided on at least the surface of the lens bodycan be, for example, a polyhydric alcohol with at least five pendanthydroxyl groups. In one example, the polyhydric alcohol with at leastfive pendant hydroxyl groups is a polyhydric alcohol with at least fivependant hydroxyl groups wherein two of the pendant hydroxyl groups areattached to the first and the third carbon in a chain (i.e., thepolyhydric alcohol is a 1,3 polyol with at least 3 additional hydroxylgroups attached to the chain after the 3 position, such as, for example,on a 9 or more carbon chain, in the 5 position, the 7 position and the 9position, etc.).

The polyhydric alcohol provided on at least the surface of the lens bodycan be, in yet another example, a polyhydric alcohol with at least 5pendant hydroxyl groups, wherein at least two of the hydroxyl groups arepositioned on a chain of more than 3 carbon atoms such that there is onecarbon atom without a hydroxyl group bonded to it between two carbonseach having one hydroxyl group bonded to them. For example, thepolyhydric alcohol with at least 5 pendant hydroxyl groups can have thefirst two hydroxyl groups bonded to the 2^(nd) and 4^(th) carbons of thecarbon chain, with the remaining at least 3 hydroxyl groups bonded tothe 5^(th) carbon, the 6^(th) carbon, the 7^(th) carbon, etc. Thepolyhydric alcohol can be a polyhydric alcohol with at least 5 pendanthydroxyl groups, wherein the at least five of the hydroxyl groups arebonded anywhere along the carbon chain such that one carbon without ahydroxyl group bonded to it is present between each carbon with onehydroxyl group bonded to it. The polyhydric alcohol can be a polyhydricalcohol with at least five pendant hydroxyl groups, wherein at least twoof the hydroxyl groups are positioned on a chain of more than 3 carbonatoms such that there is one carbon atom without a hydroxyl group bondedto it, the carbon atom positioned between two carbon atoms, each of thetwo carbon atoms having one hydroxyl group bonded to them, and whereinnone of the remaining 3 hydroxyl groups are in the geminal position orin the vicinal position with respect to each other and to the first twohydroxyl groups.

The polyhydric alcohol provided on at least the surface of the lens bodycan be, for example, a polyhydric alcohol having at least five pendanthydroxyl groups, such as a polyhydric alcohol having at least five, orsix, or seven, or eight, or nine, or ten, or eleven or more, pendanthydroxyl groups. The indicated number of hydroxyl groups refers to thehydroxyl groups present in the polyhydric alcohol as attached to theophthalmically acceptable acid in the lens body. The polyhydric alcoholwith at least five pendant hydroxyl groups can have a weight averagemolecular weight of at least 10,000, at least 50,000, at least 100,000,or at least 125,000 (e.g., about 10,000 to about 500,000, about 50,000to about 300,000, or about 50,000 to about 200,000).

The polyhydric alcohol having at least five pendant hydroxyl groups canbe a form of polyvinyl alcohol. The polyvinyl alcohol can have a weightaverage molecular weight in the range of from about 4,000 to about300,000 Daltons, or in the range of about 60,000 to about 210,000Daltons, or in the range of about 80,000 to about 150,000 Daltons orhigher, or in the range from about 120,000 to about 210,000 Daltons, orin the range from about 140,000 to about 190,000 Daltons. The polyvinylalcohol can be hydrolyzed to an extent, for example, of at least 50%(mole %), at least 88% (mole %) or at least 98% hydrolyzed (mole %)(e.g., 50% to 99.9%, 70% to 99%, 75% to 99.5% (mole %)). At least oneform of polyvinyl alcohol can be used having a viscosity of, forexample, from about 50 centipoise to about 70 centipoise, such asdetermined using the falling ball method in a 4% solution in water at20° C.

Polyvinyl alcohols typically are manufactured by polymerization of vinylacetate, which unlike vinyl alcohol, is stable. The polyvinyl acetateproduced then undergoes alcoholysis. As the technical properties ofpolyvinyl alcohol depend in the first place on the molar mass andresidual acetyl group content, industrial manufacturing processes aredesigned to ensure exact adherence to these parameters. As polyvinylalcohols are commonly prepared by partial or complete hydrolysis ofpolyvinyl acetate to remove acetate groups, polyvinyl alcohols arecommonly divided into two types based on the level of hydrolysisachieved in the final PVOH product, i.e., partially hydrolyzed and fullyhydrolyzed types, depending upon the mole percentage (mol %) of residualacetate groups that remain in the molecule after polyvinyl acetate hasbeen hydrolyzed to polyvinyl alcohol.

The polyhydric alcohol component can comprise a mixture of two or morepolyhydric alcohols. The mixture can be a mixture of two or more typesof polyhydric alcohols, such as a polyvinyl alcohol and a differentpolyhydric alcohol. The mixture can be a mixture of two or morepolyhydric alcohols of the same type having different average molecularweights such as, for example, a polyvinyl alcohol with an averagemolecular weight of about 100,000 Daltons and a polyvinyl alcohol withan average molecular weight of about 200,000 Daltons. The mixture can bea mixture of two or more polyhydric alcohols with different viscosities.The mixture can be a mixture of two or more polyhydric alcohols withdifferent levels of hydrolysis, such as, for example, a polyvinylalcohol with a hydrolysis level of 89% and a polyvinyl alcohol with ahydrolysis level of 98%. When the mixture of two or more polyhydricalcohols is a mixture of two polyhydric alcohols, the two polyhydricalcohols can be present at a ratio of about 95:5 (w:w), about 90:10(w:w), about 80:20 (w:w), about 70:30 (w:w), about 60:40 (w:w), or about50:50 (w:w).

Although in practice water is generally the solvent used for PVOH, anumber of other suitable solvents or solvent mixtures do exist. Whilethe solution can be free of solvents other than water, it is understoodthat other solvents may be used in place of, or in conjunction withwater. For example, the solvent can be a buffer, such as, for example,phosphate buffered saline (PBS), including 30 mM PBS. PVOH solutions canbe used in the present invention for wetting or soaking contact lensesand can have a PVOH concentration from about 0.01 (w/w) to about 15%(w/w), or from about 0.05% (w/w) to about 5% (w/w), or from about 0.1%(w/w) to about 3% (w/w). An example of a PVOH solution is an aqueous orsaline solution with at least 0.05% (w/w) PVOH. Another example of a PVAsolution is an aqueous solution of from about 0.25 (w/w) to about 1%(wt/wt) MOLWIOL 40-88 PVA, commercially available from Kuraray (Houston,Tex., USA). Other PVOH concentrations also may be suitable. However, itis recognized that the optimal concentration can depend on the grade ofPVOH, the molecular weight of the PVOH, or both. Such concentrationswill be apparent or easily determinable by those of skill in the artthrough routine experimentation.

In one example, the PVOH solution can include boric acid. The presenceof the boric acid causes the PVOH to gel, thereby increasing theviscosity of the solution. While not being bound by any theory, it isbelieved that including boric acid in the solution may cause the PVOH toat least partially crosslink to itself, thus making it possible toincrease the thickness of the “layer” of PVOH which can adhere to thelens. Additionally, it is believed that crosslinked PVOH migrates fromthe lens surface into the bulk of the lens to a lesser extent ascompared to non-crosslinked PVOH. Depending upon the lens formulationand the form of PVOH used for surface treatment, migration of PVOH fromthe lens surface into the bulk of the lens can produce changes in someproperties of the lens body such as, for example, modulus, and tensilestrength, and also lens shape. Instead of adhering single “strands” ofPVOH to the lens, multiple “strands” of at least partially crosslinkedPVOH can be adhered to the lens, thus increasing the “depth” of thelayer of PVOH on the lens, and making it more difficult for the bulkiercrosslinked PVOH to migrate into the lens body. For example, boric acidcan be included at a concentration of between 0.0005% (w/w) and 1%,(w/w) or between about 0.01% (w/w) and about 0.2% (w/w), in a solutionof PVOH.

In another example, the PVOH solution can include a second polymer. Thesecond polymer can include, for example, a form of polyvinylpyrrolidone, a polymeric form of phosphoryl choline, such as, forexample, 2-methacryloyloxy ethyl phosphorylcholine (MPC, HEMA-PC), or apolymeric form of hydroxyl propyl methyl cellulose (HPMC). Mixing PVOHand a second polymer can result in the two polymers becoming entangled.The PVOH and second polymer solution can be heated to increase the levelof entanglement. As the second polymer is entangled with the PVOH, whenthe solution is used to treat at least the surface of a lens bodycontaining an ophthalmically acceptable acid, when the PVOH attaches tothe ophthalmic acid, the entangled second polymer will be attached aswell.

FIGS. 1A, 1B, 1C and 1D are non-limiting schematics of formation of alayer of a polyol on a surface comprising a polymerized lens bodycontaining an ophthamically acceptable acid, wherein a polyvinyl alcoholhaving five or more hydroxyl groups is attached to a polymer of4-vinylphenyl boronic acid (VPB). As shown in FIG. 1A, a form ofvinylphenyl boronic acid is reacted to form a polymerized reactionproduct, for example, a contact lens body. The lens body is shown withboronic acid groups present on the surface of the lens body. The boronicacid can be polymerically bonded and thus be part of the polymer matrixof the lens body. Alternatively, the boronic acid can be anon-polymerizable form that is dispersed in the monomer mix that isreacted to form the lens body, thereby trapping the dispersed acid inthe polymerized lens body. The lens body is then contacted with asolution containing a polyol, for example a polyvinyl alcohol having atleast five pendant hydroxyl groups. As shown in FIG. 1A, PVOH moleculesare then attached to the boronic acid groups on at least the surface ofthe lens body.

As shown in FIG. 1B, a polymerizable form of vinylphenyl boronic acid isreacted to form a lens body composed of a homopolymer of the acid in thereaction product. The lens body is then contacted with a solutioncontaining a polyvinyl alcohol having at least five pendant hydroxylgroups. As shown in FIG. 1B, PVOH chains having at least five pendanthydroxyl groups are then attached to portions of the homopolymer on atleast the surface of the lens body.

As shown in FIG. 1C, a polymerizable form of vinylphenyl boronic acid isreacted with N,N-dimethyl acrylamide (DMA) to form a lens body composedof a copolymer of the acid and DMA. The lens body is then contacted witha solution containing a polyvinyl alcohol having at least five pendanthydroxyl groups. As shown in FIG. 1C, PVOH chains having at least fivependant hydroxyl groups are then attached to portions of the copolymeron at least the surface of the lens body.

As shown in FIG. 1D, a polymerizable form of vinylphenyl boronic acid isreacted with DMA and ethylene glycol methyl ethyl methacrylate (EGMA) toform a lens body composed of a copolymer of the acid, DMA and EGMA. Thelens body is then contacted with a solution containing a polyvinylalcohol having at least five pendant hydroxyl groups. As shown in FIG.1D, PVOH chains having at least five pendant hydroxyl groups are thenattached to portions of the copolymer on at least the surface of thelens body.

In one example, the lens body can be autoclaved in the solutioncontaining the polyol. The autoclave conditions may be, for example,from about 100° C. to about 150° C. for a time period of from about 20minutes to about 40 minutes, or may be from about 110° C. to about 130°C. for a time period of from about 25 minutes to about 35 minutes.

Silicone Hydrogel Lens Formulations. A silicone hydrogel lensformulation comprises at least one silicone-containing component that iscompatible with the ophthalmically acceptable acid, the at least onehydrophilic monomer, the at least one crosslinking agent, and thepolyhydric alcohol at the lens surface. With respect to polymerizablelens formulations as discussed herein, “compatible” components refer tocomponents which, when present in a polymerizable composition prior topolymerization, form a single phase that is stable for a duration oftime adequate to allow manufacture of a polymerized lens body from thecomposition. For some components, a range of concentrations may be foundto be compatible. Additionally, “compatible” components are componentswhich, when polymerized to form a polymerized lens body, produce a lensthat has adequate physical characteristics to be used as a contact lens(e.g., adequate transparency, modulus, tensile strength, etc.)

Silicone-containing component. The Si and attached O portion (Si—Oportion) of the silicone-containing component can be present in thesilicone-containing component in an amount greater than 20% (w/w), forexample greater than 30% (w/w), of the total molecular weight of thesilicone-containing component. Useful silicone-containing componentscomprise polymerizable functional groups such as acrylate, methacrylate,acrylamide, methacrylamide, N-vinyl lactam, N-vinylamide, and styrylfunctional groups. Silicone hydrogel contact lenses produced asdescribed herein can be based on a silicone-containing monomer and ahydrophilic monomer or co-monomer. In addition to thesilicone-containing compounds represented by formula (I) describedherein, examples of other silicone-containing components that may beuseful in the present lenses can be found in U.S. Pat. Nos. 3,808,178,4,120,570, 4,136,250, 4,139,513, 4,153,641, 4,740,533, 5,034,461,5,496,871, 5,959,117, 5,998,498, and 5,981,675, and U.S. Pat.Application Publication Nos. 2007/0066706 A1, 2007/0296914 A1, and2008/0048350 A1, all of which are incorporated in their entiretiesherein by reference. The silicone-containing component can be asilicone-containing monomer or macromer.

A silicone-containing monomer, macromer or prepolymer can have, forexample, the following general structure (II):

where R⁵ is H or CH₃, X is O or NR⁵⁵ where R⁵⁵ is H or a monovalentalkyl group with 1 to 4 carbon atoms, a is 0 or 1, L is a divalentlinking group which comprises from 1 to 20 carbon atoms, or from 2 to 10carbon atoms, which can also optionally comprise ether and/or hydroxylgroups, for example, a polyethylene glycol chain, p can be from 1 to 10,or from 2 to 5, R₁, R₂, and R₃ can be the same or different and aregroups independently selected from hydrocarbon groups having 1 to about12 carbon atoms (e.g., methyl groups), hydrocarbon groups substitutedwith one or more fluorine atoms, a siloxanyl group, and siloxanechain-containing moieties, wherein at least one of R¹, R², and R₃comprises at least one siloxane unit (—OSi). For example, at least ofone of R₁, R₂, and R₃ can comprise —OSi(CH₃)₃ and/or —OSi (R⁵²R⁵³R⁵⁴)where R⁵², R⁵³ R⁵⁴ are independently ethyl, methyl, benzyl, phenyl or amonovalent siloxane chain comprising from 1 to about 100, or from about1 to about 50, or from about 1 to about 20, repeating Si—O units.

One, two, or all three of R₁, R₂, and R₃ can also comprise othersiloxanyl groups or siloxane chain-containing moieties. The combinedlinkage of —X-L-, where present in a silicone-containing monomer,macromer or prepolymer of structure (II), can contain one or moreheteroatoms that are either O or N. The combined linkage can be straightchain or branched, where carbon chain segments thereof can be straightchain. The combined linkage of —X-L- can optionally contain one or morefunctional groups selected from, e.g., carboxyl, amide, carbamate, andcarbonate. Examples of such combined linkages are provided, for example,in U.S. Pat. No. 5,998,498 and U.S. Pat. Application Publication Nos.2007/0066706 A1, 2007/0296914 A1, and 2008/0048350, all the disclosuresof which are incorporated herein by reference. The silicone-containingmonomer, macromer or prepolymer of the present invention can comprise asingle acryloyl group, such as shown in structure (II), or optionallycan possess two acryloyl groups, such as one at each terminus of themonomer. Combinations of both types of the silicone-containingcomponents optionally can be used in polymerizable compositions of thepresent invention.

The molecular weight of the silicone-containing monomer of structure(II) generally can range from about 200 to about 2000 Daltons, or fromabout 300 to about 1500 Daltons, or from about 500 to about 1200Daltons.

Examples of silicone-containing components of the present inventioninclude, for example, polysiloxanylalkyl(meth)acrylic monomersincluding, without limitation, methacryloxypropyltris(trimethylsiloxy)silane, pentamethyldisiloxanyl methylmethacrylate,and methyldi(trimethylsiloxy)methacryloxymethyl silane.

Specific examples of the silicone-containing components can be, forexample, 3-[tris(trimethylsilyloxy)silyl]propyl methacrylate (“Tris”available from available from Gelest, Morrisville, Pa., USA), andmonomethacryloxypropyl terminated polydimethylsiloxane (available fromGelest, Morrisville, Pa., USA). These silicone-containing components canhave an alkylene group as a divalent linkage group (e.g., —(CH₂)_(p)—)and “a” can be 0 with reference to structure (II), and at least twosiloxanyl groups. These silicone-containing components are designatedherein as Structure (A) class silicone-containing components. Exemplarynon-limiting structures of these silicone-containing components areshown as follows:

Other specific examples of silicone-containing components can be, forexample, 3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane (“SiGMA”, available from Gelest, Morrisville, Pa., USA) andmethyldi(trimethylsiloxy)sylylpropylglycerolethyl methacrylate(“SiGEMA”). These silicone-containing components include at least onehydroxyl group and at least one ether group in the divalent linkinggroup L shown in structure (II) and at least two siloxanyl groups. Thesesilicone-containing components are designated herein as Structure (B)class silicone-containing components. Additional details on this classof silicone-containing components are provided, for example, in U.S.Pat. No. 4,139,513, which is incorporated in its entirety herein byreference. SiGMA, for example, can be represented by the followingexemplary non-limiting structure:

Silicone-containing components of Structures (A) and (B) can be usedindividually or in any combinations thereof in polymerizablecompositions of the present invention. Silicone-containing components ofstructures (A) and/or (B) are further used in combination with at leastone silicone-free hydrophilic monomer, such as described herein. If usedin combination, for example, the amount of silicone-containing monomersof Structure (A) can be, for example, from about 10% (w/w) to about 40%(w/w), or from about 15% (w/w) to about 35% (w/w), or from about 18%(w/w) to about 30% (w/w). The amount of silicone-containing componentsof Structure (B) can be, for example, from about 10% (w/w) to about 45%(w/w), or from about 15% (w/w) to about 40% (w/w), or from about 20%(w/w) to about 35% (w/w).

Other silicone-containing components also can be used. For example,other suitable types can include, for example, poly(organosiloxane)pre-polymer such as α,ω-bismethacryloxy-propyl polydimethylsiloxane.Another example is mPDMS (monomethacryloxypropyl terminated mono-n-butylterminated polydimethylsiloxane). Other useful silicone-containingcomponents include silicone-containing vinyl carbonate or vinylcarbamate monomers including, without limitation,1,3-bis[4-(vinyloxycarb-onyloxy)but-1-yl]tetramethylisiloxane3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxysilane],3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate,3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate;trimethylsilylethyl vinyl carbonate, and trimethylsilylmethyl vinylcarbonate. Examples of one or more of these silicone-containingcomponents can be provided, for example, in U.S. Pat. No. 5,998,498 andU.S. Pat. Application Publication Nos. 2007/0066706 A1, 2007/0296914 A1,and 2008/0048350, all the disclosures of which are incorporated hereinby reference.

Silicone-Free Monomers. Hydrophilic silicone-free monomers are includedin the polymerizable compositions used to make the present contactlenses. The silicone-free monomers exclude hydrophilic compounds thatcontain one or more silicon atoms. Hydrophilic silicone-free monomerscan be used in combination with silicone-containing monomers in thepolymerizable compositions to form silicone hydrogels. Hydrophilicsilicone-free monomers can be used in combination with othersilicone-free monomers, including silicone-free hydrophilic monomers andsilicone-free hydrophobic monomers, in the polymerizable compositions toform silicon-free hydrogels. In silicone hydrogels, hydrophilicsilicone-free monomer components include those that are capable ofproviding at least about 10% (w/w), or even at least about 25% (w/w)water content to the resulting hydrated lens when combined with theother polymerizable composition components. For silicone hydrogels, thetotal silicone-free monomers can be from about 25% (w/w) to about 75%(w/w), or from about 35% (w/w) to about 65% (w/w), or from about 40%(w/w) to about 60% (w/w), of the polymerizable composition.

Monomers that may be included as the silicone-free monomers typicallypossess at least one polymerizable double bond and at least onehydrophilic functional group. Examples of polymerizable double bondsinclude, for example, vinyl, acrylic, methacrylic, acrylamido,methacrylamido, fumaric, maleic, styryl, isopropenylphenyl,O-vinylcarbonate, O-vinylcarbamate, allylic, O-vinylacetyl and N-vinyllactam and N-vinylamido double bonds. In one example, the hydrophilicmonomers are vinyl-containing (e.g., an acrylic containing monomer or anon-acrylic vinyl containing monomer). Such hydrophilic monomers maythemselves be used as crosslinking agents.

Such hydrophilic silicone-free monomers may be but are not necessarilycrosslinking agents. Considered as a subset of acryloyl moieties asdescribed above, an “acrylic-type” or “acrylic-containing” oracrylate-containing monomer is a monomer containing the acrylic group(CR′H═CRCOX) wherein R is H or CH₃, R′ is H, alkyl, or carbonyl, and Xis O or N, which are also known to polymerize readily.

For silicone hydrogels, the hydrophilic silicone-free component cancomprise non-silicon containing monomer components comprising an acrylicmonomer (e.g., a monomer with a vinyl group at the α-carbon position anda carboxylic acid terminus, a monomer with a vinyl group at the α-carbonposition and an amide terminus, etc.) and hydrophilic vinyl-containing(CH₂═CH—) monomer (i.e., a monomer containing a vinyl group that is notpart of an acrylic group).

Illustrative acrylic monomers include N,N-dimethylacrylamide (DMA),2-hydroxyethyl acrylate, glycerol methacrylate, 2-hydroxyethylmethacrylate (HEMA), methacrylic acid, acrylic acid, methylmethacrylate(MMA), ethylene glycol methyl ether methacrylate (EGMA) and any mixturesthereof. In one example, the total acrylic monomer content is in anamount ranging from about 5% (w/w) to about 50% (w/w) of thepolymerizable composition used to prepare a silicone hydrogel lensproduct, and can be present in an amount ranging from about 10% (w/w) toabout 40% (w/w), or from about 15% (w/w) to about 30% (w/w), of thepolymerizable composition.

As described above, the silicone-free monomers also can comprise ahydrophilic vinyl-containing monomer. Hydrophilic vinyl-containingmonomers that may be incorporated into the materials of the presentlenses include the following: N-vinyl lactams (e.g. N-vinyl pyrrolidone(NVP)), N-vinyl-N-methyl acetamide (VMA), N-vinyl-N-ethyl acetamide,N-vinyl-N-ethyl formamide, N-vinyl formamide, N-2-hydroxyethyl vinylcarbamate, N-carboxy-β-alanine N-vinyl ester. One example of avinyl-containing monomer is N-vinyl-N-methyl acetamide (VMA). Thestructure of VMA corresponds to CH₃C(O)N(CH₃)—CH═CH₂. In one example,the total vinyl-containing monomer content of the polymerizablecomposition is in an amount ranging from about 0% to about 50% (w/w) ofthe polymerizable composition used to prepare the silicone hydrogel lensproduct, and can be present in an amount ranging from about 20% (w/w) toabout 45% (w/w), or from about 28% (w/w) to about 40% (w/w), of thepolymerizable composition. Other silicone-free lens-forming hydrophilicmonomers known in the art also may be suitable.

Crosslinking agents for the silicone hydrogels include theabove-indicated crosslinking agents. Examples of acrylate-functionalizedethylene oxide oligomers for use in crosslinking agents can includeoligo-ethylene oxide dimethacrylate. The crosslinking agent can beTEGDMA, TEGDVE, EGDMA, TMGDMA, or any combinations thereof. Typically,the crosslinking agents are present in the polymerizable siliconehydrogel composition in relatively small total amounts in thepolymerizable composition, such as in an amount ranging from about 0.1%(w/w) to about 10% (w/w), or from about 0.5% (w/w) to about 5% (w/w), orfrom about 0.75% (w/w) to about 1.5% (w/w), by weight of thepolymerizable composition.

Silicone-Free Hydrogel Lens Formulations. Hydrophilic silicone-freemonomers can be used without, or essentially without, the co-presence ofsilicone-containing monomers in polymerizable compositions used toprepare contact lenses of the present invention. A silicone-freehydrogel comprises a silicone-free monomer or monomers that arecompatible with the ophthalmically acceptable acid, any otherhydrophilic monomers and the crosslinking agent, and the polyhydricalcohol on at least the lens surface.

The silicone-free polymerizable composition can comprise, for example,one or more silicone-free monomers, for examplehydroxyalkyl(alkyl)acrylate, and units of a methacrylatephosphorylcholine-monomer, and a crosslinking agent. HEMA-basedformulations can be used. In an example formulation, hydroxyethylmethacrylate (HEMA), 2-methacryloyloxyethyl phosphorylcholine (MPC), andethylene glycol dimethacrylate (EGDMA), can be used in combination. HEMAor other hydroxyalkyl(alkyl)acrylate can be used in amounts from about50% (w/w) to about 90% (w/w), or about 65% (w/w) to about 80% (w/w), orabout 70% (w/w) to about 80% (w/w), of the polymerizable composition.MPC or other methacrylate phosphorylcholine-monomers, HEMA, as well asother silicone-free monomers, can be used in amounts from about 3% (w/w)to about 20% (w/w), or about 6% (w/w) to about 18% (w/w), or about 9%(w/w) to about 15% (w/w) of the composition. A crosslinking agent, suchas those indicated herein, can be present in an amount ranging fromabout 0.1% (w/w) to about 5% (w/w), or from about 0.3% (w/w) to about2.5% (w/w), or from about 0.5% (w/w) to about 1% (w/w), of thepolymerizable composition.

Additional Hydrogel Components. The silicone hydrogel and silicone-freehydrogel lens polymerizable compositions described herein can alsoinclude additional components, e.g., one or more initiators, such as oneor more thermal initiators, one or more ultraviolet (UV) initiators,visible light initiators, combinations thereof, and the like, one ormore UV absorber agents or compounds, or UV radiation or energyabsorber, tinting agent, pigments, release agents, antimicrobialcompounds, and/or other additives. The term “additive” in the context ofthe present application refers to a compound or any chemical agentprovided in the present polymerizable hydrogel contact lenspolymerizable compositions or pre-extracted polymerized hydrogel contactlens products, but which is not necessary for the manufacture of ahydrogel contact lens.

The polymerizable compositions may comprise one or more initiatorcompounds, i.e., a compound capable of initiating polymerization of apolymerizable composition. Thermal initiators, i.e., initiators having a“kick-off” temperature, can be used. For instance, one exemplary thermalinitiator employed in the present polymerizable compositions of theinvention is 2,2′-azobiz(isobutyronitrile) (VAZO®-64). VAZO®-64possesses a kick-off temperature of about 62° C., which is thetemperature at which the reactive components in the polymerizablecomposition will begin to polymerize. Another thermal initiator is2,2′-azobis(2,4-dimethylpentanenitrile) (VAZO®-52), that possesses akick-off temperature of about 50° C. Yet another thermal initiator foruse in the compositions of the invention is azo-bis-isobutyronitrile(VAZO®-88), which has a kick-off temperature of about 90° C. All of theVAZO thermal initiators described herein are available from DuPont(Wilmington, Del., USA). Additional thermal initiators include nitritessuch as 1,1′-azobis(cyclohexanecarbonitrile) and2,2′-azobis(2-methylpropionitrile), as well as other types of initiatorssuch as those available from Sigma Aldrich. Ophthalmically compatiblesilicone or silicone-free hydrogel contact lenses can be obtained frompolymerizable compositions that comprise from about 0.05% (w/w) to about0.8% (w/w), or from about 0.1% (w/w) to about 0.6% (w/w), of VAZO®-64 orother thermal initiator.

A UV absorber may be, e.g., a strong UV absorber that exhibitsrelatively high absorption values in the UV-A range of about 320-380nanometers, but is relatively transparent above about 380 nm. Examplesinclude photopolymerizable hydroxybenzophenones and photopolymerizablebenzotriazoles, such as 2-hydroxy-4-acryloyloxyethoxy benzophenone,commercially available as CYASORB UV416 from Cytec Industries, WestPaterson, N.J., USA, 2-hydroxy-4-(2hydroxy-3-methacrylyloxy)propoxybenzophenone, and photopolymerizablebenzotriazoles, commercially available as NORBLOC® 7966 from Noramco,Athens, Ga., USA. Other photopolymerizable UV absorbers suitable for usein the invention include polymerizable, ethylenically unsaturatedtriazines, salicylates, aryl-substituted acrylates, and mixturesthereof. Generally speaking, a UV absorber, if present, is provided inan amount corresponding to about 0.5 weight percent of the polymerizablecomposition to about 1.5 weight percent of the composition. For example,compositions can include from about 0.6% (w/w) to about 1.0% (w/w) ofone or more UV absorbers.

The polymerizable compositions of the invention may also include atinting agent, although both tinted and clear lens products arecontemplated. In one example, the tinting agent is a reactive dye orpigment effective to provide color to the resulting lens product.Tinting agents can include, for example, VAT Blue 6(7,16-Dichloro-6,15-dihydroanthrazine-5,9,14,18-tetrone),1-Amino-4-[3-(beta-sulfatoethylsulfonyl)anilio]-2-anthraquinonesulfonicacid (C. I. Reactive Blue 19, RB-19), a copolymer of Reactive Blue 19and hydroxyethylmethacrylate (RB-19 HEMA)1,4-bis[4[(2-methacryl-oxyethyl)phenylamino]anthraquinone (Reactive Blue246, RB-246, available from Arran Chemical Company, Athlone, Ireland),1,4-Bis[(2-hydroxyethyl)amino]-9,10-anthracenedionebis(2-propenoic)ester (RB-247). Other exemplary tinting agents aredisclosed for example, in U.S. Patent Application Publication No.2008/0048350, the disclosure of which is incorporated herein byreference. Other suitable tinting agents for use in the presentinvention are phthalocyanine pigments such as phthalocyanine blue andphthalocyanine green, chromic-alumina-cobaltous oxide, chromium oxides,and various iron oxides for red, yellow, brown and black colors.Opaquing agents such as titanium dioxide may also be incorporated. Forcertain applications, a mixture of colors may be employed. If employed,tinting agents can be present in an amount ranging from about 0.1% (w/w)to about 15% (w/w), or about 1% (w/w) to about 10% (w/w), or about 4%(w/w) to about 8% (w/w).

The polymerizable compositions of the invention may also comprise ademolding aid, that is to say, one or more compounds effective in makingmore facile removal of the cured contact lenses from their molds.Exemplary demolding aids include hydrophilic silicones, polyalkyleneoxides, and combinations thereof. The polymerizable compositions mayadditionally comprise a diluent selected from the group consisting ofhexanol, ethoxyethanol, isopropanol (IPA), propanol, decanol andcombinations thereof. Diluents, if employed, are typically present inamounts ranging from about 10% (w/w) to about 30% (w/w). Compositionshaving relatively higher concentrations of diluents tend to, but do notnecessarily, have lower ionoflux values, reduced modulus, and increasedelongation, as well as WBUTs greater than 20 seconds. Additionalmaterials suitable for use in making hydrogel contact lenses aredescribed in U.S. Pat. No. 6,867,245, which are incorporated herein byreference. In certain embodiments however, the polymerizable compositionis diluent-free.

Preparation Methods for Lenses. Various processes are known for curing apolymerizable composition in the production of contact lenses, includingspincasting and static casting. Spincasting methods involve charging themonomer mixture to a mold, and spinning the mold in a controlled mannerwhile exposing the monomer mixture to UV light. Static casting methodsinvolve charging the monomer mixture between two mold sections, one moldsection shaped to form the anterior lens surface and the other moldsection shaped to form the posterior lens surface, and curing themonomer mixture by exposure to UV light, heat, visible light, or otherradiation. Additional details and methods for forming contact lenses canbe found, for example, in U.S. Patent Application Publication Nos.2007/0296914 and 2008/0048350, the disclosure of each of which isincorporated herein by reference.

After curing the reaction mixture, the resulting polymer is separatedfrom the mold. In some situations, such in static cast molding, the twomold members are first separated before separating the polymer from themold.

The resulting polymer can also be treated with a solvent to removediluent (if used), unreacted components, byproducts, and the like, andhydrate the polymer to form the hydrogel. Lenses made using the presentpolymerizable formulations do not require extraction with organicsolvents, aqueous solutions containing organic solvents, or water priorto hydration and packaging, although they can be extracted in thismanner. The solvent may be water (or an aqueous solution such asphysiological saline or an aqueous solution of a surfactant), or,depending on the solubility characteristics of the diluent and residualunpolymerized monomers, the solvent initially used can be an organicliquid such as ethanol, methanol, isopropanol, mixtures thereof, or thelike, or a mixture of one or more organic liquids with water, followedby extraction with pure water (or physiological saline or a surfactantsolution) to produce the silicone hydrogel comprising a polymer swollenwith water. The extraction process, the hydration process, or both theextraction and hydration processes can be carried out using a heatedliquid, a pressurized liquid, or a liquid under a vacuum. The siliconehydrogels after hydration can comprise 20% (w/w) to 80% (w/w) water, forexample, 30% (w/w) to 70% (w/w) water, or 40% (w/w) to 60% (w/w) waterof the total weight of the hydrogel. The silicone-free hydrogels afterhydration can comprise 20% (w/w) to 80% (w/w) water, for example, 30%(w/w) to 70% (w/w) water, or 40% (w/w) to 60% (w/w) water of the totalweight of the hydrogel.

Exemplary Polymerizable Compositions. The monomers of the presentpolymerizable compositions may be polymerized alone or copolymerizedwith other monomers to give a contact lens material.

A general formulation for contact lens materials described herein andbased on a silicone hydrogel formulation is given in Table I.

TABLE I Silicone Hydrogel Contact Lens Material Formulation ComponentExamples Wt/wt % (a) First Monomer, (Structure (B)) 10%-45% Macromer orPrepolymer (i.e., silicone-containing) (used alone or in combinationwith (b)) (b) Second Monomer, (Structure (A)) 10%-40% Macromer orPrepolymer (i.e., silicone containing) (used alone or in combinationwith (a)) (c) Silicone-free Monomer (See Table II) 30%-90% (i.e.,hydrophilic) (d) Cross-linking Agent (See Table III)  0%-10% (e)Polymerization Initiator (See Table IV) 0%-5% (f) Ophthamicallyacceptable (See Table V) 0.1%-10%  acid

TABLE II Silicone-free Co-monomers N,N-dimethylacrylamide “DMA” Methylmethacrylate “MMA” N-vinyl-N-methylacetamide “VMA” ethylene glycolmethyl ether methacrylate “EGMA” methoxy polyethyleneglycol methacrylate“MPEGMA”

TABLE III Crosslinkers triethyleneglycol dimethacrylate “TEGDMA”ethyleneglycol dimethacrylate “EGDMA” triallyl isocyanurate “TAIC”trimethylene glycol dimethacrylate “TMGDMA” triethylene glycol divinylether “TEGDVE” vinyl methacrylate “VM” pentaerythritol triacrylate “PTA”trimethylolpropane trimethacrylate “TPTMA”

TABLE IV Polymerization Initiators2,2′-azobis(2,4-dimethylpentanenitrile) “VAZO-52”2,2′-azobis(2-methylpropanenitrile) “VAZO-64”

TABLE V Ophthamically Acceptable Acid 4-vinylphenyl boronic acid “VPB”

Copolymers can be prepared by combining one or more silicone containingmonomers, macromers or prepolymers, for example first and secondsilicone-containing monomers, such as combining Structure (A) and (B)monomers, with one or more silicone-free co-monomers, such as thosedescribed in Table II and a cross-linking agent, such as those describedin Table III. The ophthamically acceptable acid of Table V and apolymerization initiator, such as those described in Table IV, is addedto the mixture.

The copolymers are prepared in the form of contact lenses using suitablelens molds, or in the form of films made between Teflon-lined glassslides, by first combining the components listed in Table I. The monomermixtures are dispensed into molds or the slide cavities and then theinitiator is “kicked-off”, for example, by heating to the appropriatekick-off temperature. After completion of molding, the molds are opened,and the lenses are separated from the molds. The lenses are thencontacted with a polyhydric alcohol solution. The lenses can be hydratedin an aqueous solution prior to treatment with the polyhydric alcoholsolution. Optionally, the lenses can be extracted in an organic solvent,such as, for example, a volatile alcohol, an aqueous solution of anorganic solvent, or in an aqueous solution or water prior to hydration.In one method, the lenses can be autoclaved in an aqueous solution ofthe polyhydric alcohol, and then can be packaged in blisters or blisterpacks, such as blisters using a PBS solution.

A general formulation for the contact lens materials based on asilicone-free hydrogel formulation is given in Table VI.

TABLE VI Silicone-free Hydrogel Contact Lens Material FormulationComponent wt/wt % (a) First Silicone-free Co- HEMA 50%-90%  monomer(i.e., hydrophilic) (b) Optional Second (See Table II) 3%-20%Silicone-free Co-monomer (i.e., hydrophilic) (c) Cross-linking Agent(See Table III) 0%-10% (d) Polymerization Initiator (See Table IV)0%-5%  (e) Ophthamically acceptable (See Table V) 0.1%-10%   acid (f)Tinting agent VAT Blue 6 0%-15%

Contact lenses made with the present formulations can have enhancedwettability as shown, for example, by various properties thereof suchas, for example, contact angle, water break up time (WBUT), take up ofwetting solution, and others.

Properties of the Lenses. The lens surface of contact lenses can have anadvancing contact angle of less than 100°, or less than 80°, or lessthan 70°, or less than 60°, or less than 50°. The advancing contactangle of the lens surface remains less than about 100° after about sixhours, or after about 24 hours, or after about 48 hours, of storage in apackaging solution free of a form of polyhydric alcohol which is apolyol with at least 5 pendant hydroxyl groups, including a 1,3 polyolwith at least 5 pendant hydroxyl groups.

The lens surface has a water break up time (WBUT) of greater than fiveseconds, or at least 10 seconds, or at least 15 seconds, or at least 20seconds.

The lens surface can maintain an advancing contact angle of less than100° and the water break up time of greater than five seconds followingin vitro testing for duration of at least 6 hours, or at least 12 hours,or at least 24 hours, or at least 48 hours.

At least 30%, or at least 45%, or at least 60%, of the at least one formof polyhydric alcohol that is initially present onto the lens surfaceremains in place after at least 6 hours, or at least 12 hours, or least24 hours, or at least 48 hours, of in vitro testing, and after at least6 hours, or at least 12 hours, of in vivo testing.

At least 50%, or least 60%, or at least 70%, or at least 80% (e.g., 50%to 99.9%, 60% to 95%, 70% to 90%, 75% to 95%, 80% to 99%, 85% to 99%) byweight of the ophthalmically acceptable acid originally present in thepolymerizable composition remains present in the lens body and/or on thelens surface after about six hours, or after 12 hours, or after 24hours, or after 48 hours, based on in vitro testing.

Contact lens package. A contact lens package is provided comprising thecontact lens body, such as described above, and a packaging solutioncomprising another polyhydric alcohol, such as a polyhydric alcohol withat least five pendant hydroxyl groups. When a polyhydric alcohol ispresent on the lens surface, is present in the packaging solution, orboth, the lenses have been found not to stick to packaging components.The polyhydric alcohol provided on the surface of the lens body and thepolyhydric alcohol of the packaging solution can be the same ordifferent. The different polyhydric alcohols can have the same ordifferent average molecular weights. One or both of the differentpolyhydric alcohols can be, for example, forms of polyvinyl alcohol. Thepolyhydric alcohol, such as the polyhydric alcohol with at least fivependant hydroxyl groups, can be present in the packaging solution at aconcentration, for example, of at least about 0.001% (w/w), or at leastabout 0.01%, or at least about 0.1%, or at least about 0.25% (w/w), orat least about 0.5% (w/w), or at least about 1% (w/w), or at least about2% (w/w), by weight (e.g., from about 0.001% to about 5%, the upperlimit being dictated by the viscosity of the solution).

With respect to the contact lens package, the package can furthercomprise a base member with a cavity configured to hold the contact lensbody and the packaging solution, and a seal attached to the base memberconfigured to maintain the contact lens and the packaging solution in asterile condition for a duration of time equivalent to a shelf life ofthe contact lens. The contact lens body does not adhere to the basemember or the seal, or the contact lens body adheres less frequently tothe base member or the seal as compared with a substantially identicalcontact lens body without the polyhydric alcohol, for example apolyhydric alcohol with at least five pendant hydroxyl groups present onthe lens surface. The contact lens body does not adhere to the basemember or the seal, or the contact lens body adheres less frequently tothe base member or the seal as compared with a substantially identicalcontact lens body without the polyhydric alcohol with at least fivependant hydroxyl groups present in the packaging solution.

Rewetting (recharging) the lenses. After a contact lens as describedherein is worn by a user or is otherwise used in a manner wherein thepolyhydric alcohol is lost at the modified lens surface, the lens can berecharged with a polyhydric alcohol wetting aid at least the lenssurface by soaking or immersing (submerging) the lens body in an aqueoussolution comprising a polyhydric alcohol, such as a polyhydric alcoholwith at least five pendant hydroxyl groups. Soaking the lens bodyovernight (approx. 9-12 hours) at room temperature can be sufficient torecharge the surfaces of the lens adequately so that the lens again hasan ophthalmically acceptable wettable surface.

As previously discussed, in another example of the present invention,the ophthalmically acceptable acid comprises at least one form of aboronic acid, boronic ester, boronic anhydride, or combination thereof.The at least one form of a boronic acid, boronic ester, boronicanhydride or combinations thereof is present in a lens body. The atleast one form of a boronic acid, boronic ester or boronic anhydride cancomprise a polymerizable form of the boronic acid, boronic ester,boronic anhydride, or combination thereof. The polymerizable form of theboronic acid, boronic ester, boronic anhydride, or combination thereof,instead of or in addition to being distributed as a second polymercomponent in the reaction product, can be present as a polymerizablecomponent of the polymerizable composition, and, after polymerization,can be present as polymerized units of the copolymer that forms the lensbody.

In this example, the lens body that is the polymerized reaction productcan have at least one polyhydric alcohol present on at least one lenssurface, i.e., the lens body may comprise a complexed lens body. The atleast one polyhydric alcohol present on at least one lens surface may bepresent on both the anterior lens surface and the posterior lenssurface. The at least one polyhydric alcohol may be present in the bulkof the lens body as well as on a lens surface. The polyhydric alcoholcan comprise a polyhydric alcohol having at least one 1,3 diol moiety(i.e., a polyhydric alcohol with a backbone comprising at least threecarbon atoms, the at least three carbon atoms bonded in a chain as aright carbon atom bonded to a center carbon atom, the center carbon atombonded to a left carbon atom, wherein one and only one hydroxyl group isbonded to the right carbon atom, a hydroxyl group is not bonded to thecenter carbon atom, and one and only one hydroxyl group is bonded to theleft carbon atom). Additionally, the polyhydric alcohol can comprise apolyhydric alcohol having at least one 1, 2 diol moiety, or having botha 1, 2 diol and a 1,3 diol moiety. In the example where the polyhydricalcohol is a polyhydric alcohol having at least one 1, 2 diol or 1,3diol moiety, at least a portion of 1, 2 diol or 1,3 diol moietiespresent in the polyhydric alcohol can be complexed with at least aportion of boronic acid moieties present in the copolymer of the lensbody (e.g., boronic acid moieties present on a lens surface, within thebulk of the lens body, or both). Alternatively, boronic acid moietiespresent in the copolymer of the lens body may not be complexed with 1, 2or 1,3 moieties of a polyhydric alcohol, i.e., the lens body that is thepolymerized reaction product may be an uncomplexed lens body. In oneparticular example, the uncomplexed lens body can be contacted with asolution of a polyhydric alcohol having 1, 2 diol or 1,3 diol moieties,and at least a portion of boronic acid moieties present in the copolymerof the lens body can complex with at least a portion of 1, 2 diol or 1,3diol moieties present in the polyhydric alcohol solution, forming acomplexed lens body.

The example can comprise a method of manufacturing a hydrogel contactlens body. The method of manufacturing a hydrogel contact lens body cancomprise: (i) providing a lens body comprising at least one form ofboronic acid, boronic ester, boronic anhydride or combination thereof;and (ii) contacting the lens body with a contacting solution comprisingat least one form of tris(hydroxymethyl)aminomethane (TRIS).

The at least one form of the boronic acid, boronic ester, boronicanhydride or combination thereof can comprise a polymerizable form ofthe at least one form of the boronic acid, boronic ester, boronicanhydride or combination thereof. The at least one polymerizable form ofthe boronic acid, boronic ester, boronic anhydride or combinationthereof can comprise a polymerizable form of boronic acid, apolymerizable form of boronic anhydride, or a combination of apolymerizable form of boronic acid and a polymerizable form of boronicanhydride. The at least one polymerizable form of the boronic acid,boronic ester, boronic anhydride or combination thereof can comprise aboronic acid. The at least one polymerizable form of the boronic acid,boronic ester, boronic anhydride or combination thereof can comprise apolymerizable form of a boronic acid. The at least one polymerizableform of the boronic acid, boronic ester, boronic anhydride orcombination thereof can comprise a vinylphenyl boronic acid, forexample, 2-vinylphenyl boronic acid, 3-vinylphenyl boronic acid,4-vinylphenyl boronic acid, or a combination thereof. The at least onepolymerizable form of the boronic acid, boronic ester, boronic anhydrideor combination thereof can comprise a polymerizable form of boronic acidhaving the structure:

The at least one form of boronic acid, boronic ester, boronic anhydrideor combination thereof can be present on at least a surface of the lensbody, can be present on both the anterior and posterior surfaces of thelens body, can be present within the bulk of the lens body, andcombinations thereof.

The lens body can comprise a hydrogel lens body. The hydrogel lens bodycan comprise a polymerized reaction product of a polymerizablecomposition, the polymerizable composition comprising at least onehydrophilic monomer, and at least one crosslinking agent; and thepolymerized reaction product comprising a polymer formed of polymerizedunits of the at least one hydrophilic monomer, and crosslinks formed bythe at least one crosslinking agent.

When the at least one form of a boronic acid, boronic ester, boronicanhydride, or combination thereof comprises a polymerizable form of theboronic acid, boronic ester, boronic anhydride, or combination thereof,the hydrogel lens body can be a polymerized reaction product of apolymerizable composition, the polymerizable composition comprising theat least one polymerizable form of the boronic acid, boronic ester,boronic anhydride, or combination thereof; at least one hydrophilicmonomer; and at least one crosslinking agent; and the polymerizedreaction product comprising a copolymer formed of polymerized units ofthe at least one polymerizable form of the boronic acid, boronic ester,boronic anhydride or combination thereof, polymerized units of the atleast one hydrophilic monomer, and crosslinks formed by the at least onecrosslinking agent.

The lens body (e.g., a complexed lens body or an uncomplexed lens body)can have an advancing contact angle less than about 120°, a modulus lessthan about 1.6 MPa, an ionoflux less than about 7×10⁻³ mm²/min., anoxygen permeability of less than about 120 Barrers, and an equilibriumwater content of at least about 30%.

In another example, the lens body (e.g., an uncomplexed lens body or acomplexed lens body) can have an advancing contact angle less than about100°, a modulus from about 0.3 MPa to about 1.0 MPa, an ionoflux lessthan about 5×10⁻³ mm²/min., an oxygen permeability of less than about110 Barrers, and an equilibrium water content from about 35% to 65%.

In yet another example, the lens body (e.g., a complexed lens body or anuncomplexed lens body) can have an advancing contact angle less thanabout 60°, a modulus from about 0.4 MPa to about 0.7 MPa, an ionofluxless than about 4×10⁻³ mm²/min., an oxygen permeability from about 55Barrers to about 100 Barrers, and an equilibrium water content fromabout 40% to 65%.

The at least one form of the boronic acid, boronic ester, boronicanhydride or combination thereof can be present in the polymerizablecomposition at a concentration from about 0.1% to about 10.0%, fromabout 0.5% to about 5.0%, for from about 1.0 to about 2.0%.

The at least one hydrophilic monomer of the polymerizable compositioncan comprise a hydrophilic monomer having at least one vinyl moiety. Theat least one hydrophilic monomer of the polymerizable composition cancomprise a plurality of hydrophilic monomers. In one example, theplurality of hydrophilic monomers can comprise a first hydrophilicmonomer having at least one vinyl moiety, and a second hydrophilicmonomer having at least one methacrylate moiety.

The at least one crosslinking agent of the polymerizable can comprise acrosslinking agent having at least one vinyl moiety. The at least onecrosslinking agent of the polymerizable composition can comprise aplurality of crosslinking agents. In one example, the plurality ofcrosslinking agents can comprise a first crosslinking agent having atleast one vinyl moiety, and a second crosslinking agent having at leastone methacrylate moiety.

The polymerizable composition can further comprise water. The water canbe present in the polymerizable composition in a molar ratio of oneboronic acid moiety to 3 water molecules. The water can be present inthe polymerizable composition in an amount effective to convert ananhydrous cyclic trimer of boronic acid moieties into three separateboronic acid moieties. As trace amounts of water may already be presentin components of the polymerizable composition, the amount of additionalwater required in the polymerizable composition in order for the a molarratio of 1:3 to be present can be determined, for example, using a KarlFischer technique. In one example, the anhydrous cyclic trimer ofstructure III present in the polymerizable composition can be convertedinto three separate boronic acid moieties of structure IV:

The polymerizable composition can further comprise at least onesilicone-containing monomer, macromer or prepolymer. In this example,the presence of a polymerizable silicone-containing compound in thepolymerizable composition results in the presence of polymerized unitsof the silicone-containing compound in the copolymer of the lens body,i.e., the copolymer further comprises polymerized units of the at leastone silicone-containing monomer, macromer or prepolymer, and theuncomplexed hydrogel contact lens body comprises an uncomplexed siliconehydrogel contact lens body. The silicone-containing monomer, macromer orprepolymer can comprise a silicone-containing macromer or prepolymer.

The silicone-containing monomer, macromer or prepolymer can have anaverage molecular weight greater than about 1,000 Daltons, greater thanabout 2,500 Daltons, greater than about 5,000 Daltons, greater thanabout 7,000 Daltons, greater than about 9,000 Daltons, greater thanabout 10,000 Daltons, or greater than about 12,000 Daltons. The averagemolecular weight can be a weight average molecular weight determined bynuclear magnetic resonance (NMR).

The silicone-containing monomer, macromer or prepolymer can comprise asilicone-containing monomer, macromer or prepolymer having ethyleneoxide (EO) units present in the backbone, the side chains, or both thebackbone and the side chains of the monomer, macromer or prepolymer. Thesilicone-containing monomer, macromer or prepolymer can comprise atleast about 10, at least about 15, at least about 20, at least about 25,at least about 30, at least about 35, or at least about 40 ethyleneoxide (EO) units.

The silicone-containing monomer, macromer or prepolymer can comprise asilicone-containing monomer, macromer or prepolymer having at leastabout 10, at least about 50, at least about 80, at least about 90, or atleast about 100 dimethyl siloxane (DMS) units present in the backbone,the side chains, or both the backbone and the side chains of themonomer, macromer or prepolymer.

When the silicone-containing compound comprises a silicone-containingmonomer, macromer or prepolymer having ethylene oxide (EO) units presentin the backbone, the side chains, or both the backbone and the sidechains of the monomer, macromer or prepolymer, the silicone-containingcompound will have a ratio of the number of ethylene oxide (EO) unitspresent to the number of dimethyl siloxane (DMS) units present. In suchan example, the ratio of the number of ethylene oxide units present tothe number of dimethyl siloxane units present (EO/DMS ratio) can be fromabout 0.20 to about 0.55, from about 0.25 to about 0.50, or from about0.35 to about 0.45.

The silicone-containing compound can comprise Silicone A, asilicone-containing component the same as, or similar in structure to,hydrophilic polysiloxane macromonomer A described in Example 2 of U.S.Patent Application Publication No. 2009/0234089 (Asahi Kasei Aime Co.,Ltd., Kanagawa, Japan).

The silicone-containing compound can comprise Silicone B, asilicone-containing component as illustrated below, and having amolecular weight of approximately 1,500 Daltons (Shin-Etsu Silicones ofAmerica, Akron, Ohio, USA).

The silicone-containing compound can comprise Silicone C, Amonomethacryloxypropyl terminated polydimethylsiloxane (Gelest,Morrisville, Pa., USA). A structure thereof is:

The silicone-containing compound can comprise a singlesilicone-containing compound or a combination of a plurality ofsilicone-containing compounds. The silicone-containing compound can bepresent in the polymerizable composition at a concentration from about1% to about 65%, from about 10% to about 60%, or from about 20% to about55%.

The polymerizable composition can further comprise at least one polymerhaving a 1, 2 diol or 1,3 diol moiety. The polymer having the 1, 2 diolor 1,3 diol moiety can comprise a polymeric wetting agent. The polymericwetting agent can form an interpenetrating polymeric network (IPN) orpseudo-IPN within the lens body.

The polymerizable composition can further comprise at least one monomerhaving a 1, 2 diol or 1,3 diol moiety. The monomer having the 1, 2 diolor 1,3 diol moiety can comprise a hydrophilic monomer. The monomer canpolymerize either as a copolymer with other components of thepolymerizable composition, or as a homopolymer. The homopolymer can forman interpenetrating polymeric network (IPN) or pseudo-IPN within thelens body.

The polymerizable composition can further comprise a non-reactivediluent. The non-reactive diluent can comprise a water-solublenon-reactive diluent, i.e., a diluent which can be extracted from thelens body using aqueous extraction media essentially free of a volatilelower alcohol. In a particular example, the water-soluble non-reactivediluent can have a 1, 2 diol or 1,3 diol moiety. The water-solublenon-reactive diluent having a 1, 2 diol or a 1,3 diol moiety can be aglycol, such as, for example, glycerin.

The polymerizable composition can further comprise a phosphorylcholinecomponent, such as, for example, 2-methacryloyloxyethylphosphorylcholine. The form of phosphorylcholine can be a polymerizableform of phosphorylcholine, or can be a polymerized form ofphosphorylcholine. The polymerizable form of phosphorylcholine or thepolymerized form of phosphorylcholine can be a crosslinkable form ofphosphorylcholine. When the phosphorylcholine component is present inthe polymerizable composition, the polymerizable composition can lackhaze or can be less hazy as compared to a comparative polymerizablecomposition of the same formulation except without the at least onepolymerizable form of a boronic acid, boronic ester, boronic anhydride,or combination thereof. The polymerizable composition comprising thephosphorylcholine component and can produce a polymerized reactionproduct that is ophthalmically acceptable transparent (i.e., is clearenough to use as a contact lens). When the phosphorylcholine componentis present in the polymerizable composition, the polymerizablecomposition can contain less than a total of 5% (w/w) of a single C₁-C₁₀monohydric alcohol diluent, or of a combination of C₁-C₁₀ monohydricalcohol diluents.

The polymerizable composition can further comprise an initiator. Theinitiator can comprise a thermal initiator, a UV initiator, or acombination of a thermal initiator and a UV initiator.

The polymerizable composition can further comprise a tinting agent, a UVblocker, or a combination thereof. The tinting agent, the UV blocker, orthe combination thereof can comprise a polymerizable tinting agent, apolymerizable UV blocker, or a combination of a polymerizable tintingagent and a polymerizable UV blocker. In the example where the tintingagent, the UV blocker, or the combination thereof comprises thepolymerizable tinting agent, the polymerizable UV blocker, or thecombination of the polymerizable tinting agent and the polymerizable UVblocker, the copolymer of the lens body further comprises polymerizedunits of the tinting agent, polymerized units of the UV blocker, orpolymerized units of the tinting agent and of the UV blocker. Thetinting agent, the UV blocker, or the combination thereof can comprise acrosslinkable tinting agent, a crosslinkable UV blocker, or acombination of a crosslinkable tinting agent and a crosslinkable UVblocker. In the example where the tinting agent, the UV blocker, or thecombination thereof comprises the crosslinkable tinting agent, thecrosslinkable UV blocker, or the combination of the crosslinkabletinting agent and the crosslinkable UV blocker, the copolymer of thelens body further comprises crosslinked units of the tinting agent,crosslinked units of the UV blocker, or crosslinked units of the tintingagent and of the UV blocker.

In the present example, the contact lens mold assembly used to cast moldthe lens body can comprise molding surfaces, including an anteriormolding surface and a posterior molding surface. At least one moldingsurface of the mold assembly can comprise a thermoplastic resin. Thethermoplastic resin can comprise a polar thermoplastic resin, anon-polar thermoplastic resin, or a combination of both a polarthermoplastic resin and a non-polar thermoplastic resin. Examples ofpolar thermoplastic resins include ethylene vinyl alcohol (EVOH) andpolybutylene terephthalate (PBT). An example of a non-polarthermoplastic resin includes polypropylene (PP). The thermoplastic resincan comprise a thermoplastic resin having at least one 1, 2 diol or 1,3diol moiety, such as, for example, PVOH. The at least one 1, 2 diol or1,3 diol moiety can be capable of complexing with at least a portion ofboronic acid moieties present in the polymerizable composition, in thepolymerized reaction product, or in both the polymerizable compositionand the polymerized reaction product.

The at least one form of tris(hydroxymethyl)aminomethane (TRIS) of thecontacting solution can comprise a TRIS buffer system. Optionally,contacting solution can further comprise at least one form ofethylenediaminetetraacetic acid (EDTA). Optionally, when the contactingsolution comprises a TRIS buffer system, the TRIS buffer system of thecontacting solution can further comprise a form ofethylenediaminetetraacetic acid (EDTA), and be a TRIS-EDTA buffersystem. The at least one form of IRIS can comprisetris(hydroxymethyl)aminomethane hydrochloride (TRIS HCl), alone or incombination with another form of TRIS. The at least one form of EDTA cancomprise ethylenediaminetetraacetic acid sodium salt dehydrate, alone orin combination with another form of EDTA.

The contacting solution can further comprise a tonicity adjusting agent,such as, for example, sodium chloride, sorbitol, mannitol, combinationsthereof, and the like. The contacting solution can have an osmolarityfrom about 100 mOsm to about 400 mOsm, from about 180 to about 350 mOsm,or from about 220 mOsm to about 320 mOsm.

The contacting solution can further comprise at least one surfactant,such as, for example, a form of polysorbate, a form of poloxomer,combinations thereof, and the like. The surfactant can comprisepolysorbate 80 (TWEEN 80).

The contacting solution can further comprise at least one wetting agentor comfort agent, such as, for example, a form of poly(vinylpyrrolidone), a form of poly(vinyl alcohol), a form of methyl ethylcellulose, a form of phosphorylcholine, combinations thereof, and thelike.

The contacting solution can further comprise at least one polyhydricalcohol having at least one 1,2 diol or 1,3 diol moiety, wherein atleast a portion of the 1, 2 diol or 1,3 diol moieties present in thesolution are capable of complexing with at least a portion of boronicacid moieties present in the lens body.

The method of this example can further comprise the step of contactingthe uncomplexed lens body with the complexing solution comprising atleast one polyhydric alcohol having at least one 1,2 diol or 1,3 diolmoiety, and complexing at least a portion of 1, 2 diol or 1,3 diolmoieties present in the complexing solution with at least a portion ofboronic acid moieties present in the copolymer of the lens body toproduce a complexed hydrogel lens body.

The complexing of the boronic acid moiety with the 1, 2 diol or 1,3 diolmoiety is equivalent to “attaching” an ophthalmically acceptable acid toPVOH, as previously discussed. The complex can be permanent orsemi-permanent, such as optionally allowing for slow release of thecomplexed polyhydric alcohol from the lens body during use, which mayenhance comfort during lens wear.

The complexed lens body of the present example can have an advancingcontact angle at least 5% less, at least 10% less, at least 15%, atleast 20%, or at least 25% less than an advancing contact angle of theuncomplexed lens when both the complexed lens body and the uncomplexedlens body are tested after being hydrated and after soaking in phosphatebuffered saline for at least 6 hours.

The complexed lens body of the present example can have an advancingcontact angle at least 5% less, at least 10% less, at least 15%, atleast 20%, or at least 25% less than an advancing contact angle of acomparative lens body made using the same polymerizable composition butwithout the at least one boronic acid, boronic ester, boronic anhydrideor combination thereof in the polymerizable composition, when both thecomplexed lens body and the comparative lens body are tested after beinghydrated and after soaking in phosphate buffered saline for at least 6hours.

As previously discussed, the polyhydric alcohol having at least one 1, 2diol or 1,3 diol moiety can comprise a form of poly(vinyl alcohol)(PVOH). The PVOH can be a crosslinked form of PVOH, such as a form ofPVOH crosslinked with boric acid, a form of PVOH crosslinked with adialdehyde or polyaldehyde, or a combination thereof.

The form of PVOH can be a form of PVOH with a low molecular weight, suchas a form of PVOH with a molecular weight below about 75,000 Daltons.The low molecular weight form of PVOH can comprise MOWIOL® 4-88(MW=31,000 Daltons) or MOWIOL® 8-88 (67,000 Daltons) (Kuraray, Houston,Tex., USA).

The form of PVOH can be a form of PVOH with a low level of hydrolysis,such as a form of PVOH with a hydrolysis level below about 90%. The formof PVOH with a low level of hydrolysis can comprise MOWIOL® 4-88 (88%hydrolyzed) or MOWIOL® 8-88 (88% hydrolyzed) (Kuraray, Houston, Tex.,USA).

The polyhydric alcohol having at least one 1, 2 diol or 1,3 diol moietyof the complexing solution can comprise catechol or a form of catechol.The form of catechol can comprise a polymerized form of catechol. Thepolyhydric alcohol can comprise glyceryl monomethacrylate (GMA), or aform of glyceryl monomethacrylate. The form of glyceryl monomethacrylatecan comprise a polymerized form of glyceryl monomethacrylate.

The polyhydric alcohol of the complexing solution can comprise a firstpolymer having at least one 1, 2 diol or 1,3 diol moiety. The firstpolymer can comprise a vinyl alcohol copolymer, a glycerylmonomethacrylate copolymer, or combinations thereof. The copolymerpolyhydric alcohol can comprise a copolymer formed of units of vinylalcohol and/or glyceryl monomethacrylate with a hydrophilic orhydrophobic monomer. The copolymer of the polyhydric alcohol can beformed of units of vinyl alcohol and/or glyceryl monomethacrylate with amonomer with a bulky side chain. The copolymer of the polyhydric alcoholwith a bulky side chain can be effective to reduce the penetration ofthe copolymer into the bulk of the lens body as compared to a vinylalcohol homopolymer of approximately the same molecular weight. Thecopolymer of the polyhydric alcohol can comprise a vinyl alcohol-vinylpyrrolidone copolymer, a vinyl alcohol-glyceryl monomethacrylatecopolymer, a vinyl alcohol-phosphorylcholine copolymer, a glycerylmonomethacrylate-vinyl pyrrolidone copolymer, a glycerylmonomethacrylate-phosphorylcholine copolymer, combinations thereof, andthe like.

The complexing solution can comprise the first polymer having the 1, 2diol or 1,3 diol moiety, and a second polymer physically entangled with(i.e., not crosslinked or chemically bonded to) the first polymer. Thefirst polymer, the second polymer, or both the first polymer and thesecond polymer can comprise a wetting agent effective to increase thewettablilty of the lens body, a comfort agent effective to increasecomfort of the lens during wear, or both.

The at least one form of TRIS can be present in the contacting solutionat a concentration effective to prevent gelation of the solution. Forexample, the at least one form of TRIS can be present in the contactingsolution at a concentration effective to prevent gelation of apolyhydric alcohol present in the solution, such as, for example, a formof PVOH.

The at least one form of TRIS can be present in the contacting solutionat a concentration effective to lower an effective pKa of boronic acidmoieties present on at least a surface of the lens body. In one example,the at least one form of TRIS present in the contacting solution can beeffective to increase the concentration of boronic acid moieties capableof complexing with 1, 2 diol or 1,3 diol moieties present in thecontacting solution by at least about 5%, at least about 15%, at leastabout 25%, or at least about 35%, at an ophthalmically acceptable pH.

In one example, the step of contacting the lens body with the contactingsolution can further comprise complexing at least a portion of boronicacid moieties present in the lens body with at least a portion of 1,2diol or 1,3 diol moieties present in solution.

The contacting and complexing step can be conducted as part of a washingor soaking process conducted prior to placing the lens body in a blisterpackage with a packaging solution. Alternatively or additionally, thecontacting and complexing step can be conducted by contacting the lensbody with a packaging solution, the packaging solution comprising acontacting solution having at least one form of TRIS and at least onepolyhydric alcohol with at least one 1, 2 diol or 1,3 diol moiety, thecontacting and complexing step being part of a step of placing the lensbody in a blister package with a packaging solution, and sealing andsterilizing the blister package.

The method can further comprise the step of washing the lens body (i.e.,the complexed lens body or the uncomplexed lens body) with a washingsolution. The step of washing the lens body can comprise contacting thelens body with water, an aqueous solution of a volatile lower alcohol,or an aqueous solution essentially free of a volatile lower alcohol. Thewashing step can comprise cleaning dust or debris from the lens body,extracting materials from the lens body, hydrating the lens body, orcombinations thereof. The washing solution can comprise a TRIS buffersystem. The washing solution can comprise the at least one polyhydricalcohol having at least one 1, 2 diol or 1,3 diol moiety. The washingsolution can be effective to clean the lens body, to extract materialsfrom the lens body, to swell the lens body, to hydrate the lens body,and combinations thereof. The step of washing can be the same step ascontacting and complexing the lens body. The step of washing can beconducted in the blister package or in a lens tray configured to hold aplurality of lenses during one or more processing steps.

The method can further comprise the step of hydrating the lens body(e.g., the complexed lens body or the uncomplexed lens body) with ahydrating solution. The hydrating solution can comprise at least oneform of TRIS. The hydrating step can comprise a separate step from thewashing step, the contacting and complexing step, or the placing step.Alternatively, the hydrating step can be incorporated into another stepof the process which involves contacting the lens body with water or anaqueous solution. The step of hydrating the lens body can comprisecontacting the lens body with water or an aqueous solution effective toswell the lens body. The aqueous solution can comprise at least onepolyhydric alcohol, the at least one polyhydric alcohol having at leastone 1, 2 diol or 1,3 diol moiety. The step of hydrating can be the samestep as complexing the lens body, the same step as placing the lens bodyin a blister package with packaging solution, or both. In other words,the lens body can be hydrated in a separate processing step, thecontacting solution can be used to hydrate the lens body, the washingsolution can be used to hydrate the lens body, the packaging solutioncan be used to hydrate the lens body, or the packaging solution can beused to hydrate the lens body, or to both complex and hydrate the lensbody.

In the method of manufacturing a hydrogel lens body of the presentexample, the method can further comprise the step of placing a lens body(i.e., a complexed lens body or an uncomplexed lens body) in a contactlens blister package with a blister solution, and sealing andsterilizing the blister package, thereby sterilizing the lens body andthe packaging solution. The blister solution can comprise at least oneform of TRIS. The at least one form of TRIS of the packaging solutioncan be the same as the at least one form of TRIS of the contactingsolution, or can be a different at least one form of TRIS. The packagingsolution can be used as the contacting solution, or can comprise adifferent solution used in a different processing step. In one example,the lens body present in the sealed, sterilized package is anuncomplexed lens body following the sealing and sterilizing (i.e.,boronic acid moieties of the copolymer of the lens body are notcomplexed with 1, 2 diol or 1,3 diol moieties of a polyhydric alcohol inthe final packaged product). In another example, the lens body presentin the sealed, sterilized package is a complexed lens body (i.e., atleast a portion of the boronic acid moieties present in the copolymer ofthe lens body are complexed with 1, 2 diol or 1,3 diol moieties of apolyhydric alcohol).

The method of this example can also comprise a method of treating a lensbody. The method of treating a lens body can comprise (i) providing alens body comprising at least one form of boronic acid, boronic ester,boronic anhydride or combination thereof; (ii) contacting the lens bodywith a contacting solution comprising at least one form oftris(hydroxymethyl)aminomethane; and (iii) contacting the uncomplexedlens body with a first complexing solution comprising at least onepolyhydric alcohol having at least one 1,2 diol or 1,3 diol moiety andcomplexing at least a portion of the at least one 1, 2 or 1,3 diolmoiety present in the first complexing solution with at least a portionof boronic acid moieties present in the copolymer of the lens body toproduce a complexed hydrogel lens body. In one example, the contactingsolution and the complexing solution can be the same solution, i.e., themethod can comprise contacting the lens body with a solution comprisingboth the at least one form of TRIS and the polyhydric alcohol having atleast one 1, 2 diol or 1,3 diol moiety.

In a particular example wherein the lens body comprises a hydrogelcontact lens, the method of treating the lens body can further comprise(iv) after the contact lens has been contacted by the first complexingsolution and subsequently worn by a user, contacting the contact lenswith a second complexing solution comprising at least one polyhydricalcohol with at least one 1,2 diol or 1,3 diol moiety, and complexing atleast a portion of 1,2 diol or 1,3 diol moieties present in the secondcomplexing solution with at least a portion of the boronic acid moietiespresent in the lens body. The second complexing solution can furthercomprise at least one form of TRIS, such as, for example, a TRIS buffersystem. The at least one form of TRIS of the second complexing solutioncan be the same as or different from the at least one form of TRIS ofthe contacting solution. The polyhydric alcohol of the first complexingsolution can be the same as the polyhydric alcohol of the secondcomplexing solution, or the polyhydric alcohol of the first complexingsolution can be different from the polyhydric alcohol of the secondcomplexing solution.

This example is also directed to a hydrogel contact lens productcomprising: a hydrogel contact lens body comprising at least one form ofboronic acid, boronic ester, boronic anhydride or combination thereof; apackaging solution comprising at least one form oftris(hydroxymethyl)aminomethane TRIS, for example, a TRIS buffer system;a contact lens package base member with a cavity configured to hold thelens body and the packaging solution; and a seal attached to the basemember configured to maintain the lens body and the packaging solutionin a sterile condition for a duration of time equivalent to a shelf lifeof the contact lens package. The lens body can comprise an anteriorsurface, a posterior surface, and at least one transparent optic zone.

The at least one form of TRIS can be present in the packaging solutionat a concentration effective to lower an effective pKa of boronic acidmoieties present on at least a surface of the lens body.

The packaging solution can further comprise at least one polyhydricalcohol having at least one 1,2 diol or 1,3 diol moiety, and at least aportion of boronic acid moieties present on at least a surface of thelens body can be complexed with at least a portion of 1,2 diol or 1,3diol moieties present on the at least one polyhydric alcohol.

The packaging solution can comprise at least one polyhydric alcoholhaving at least one 1, 2 diol or 1,3 diol moiety, and the at least oneform of TRIS can be present in the packaging solution at a concentrationeffective to prevent gelation of the packaging solution over a shelflife of the sterilized package.

The hydrogel lens body can be an uncomplexed lens body. The hydrogellens body can be a lens body wherein at least a portion of boronic acidmoieties present in the copolymer of the lens body are complexed with 1,2 or 1,3 diol moieties present on at least one polyhydric alcohol, i.e.,a complexed lens body.

The at least one polyhydric alcohol having at least one 1, 2 diol or 1,3diol moiety can be present in the contacting solution, complexingsolution, the washing solution, the hydration solution the packagingsolution, and combinations thereof, at a concentration of from about0.01% to about 10%, from about 0.05 to about 5.0%, or from about 0.1% toabout 1.0%.

The at least one form of TRIS can be present in the contacting solution,complexing solution, the washing solution, the hydration solution thepackaging solution, and combinations thereof, at a concentration of fromabout 0.01% to about 10%, from about 0.05 to about 7.0%, from about 0.5%to about 5.0%, or from about 0.3% to about 3.5%.

EXAMPLES

The following Examples illustrate certain aspects and advantages of thepresent invention, which should be understood not to be limited thereby.All parts, percentages and ratios are by weight unless indicatedotherwise.

Materials and Methods

The following abbreviations and corresponding compounds and structuresare used in the examples.

SiGMA=(3-Methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane. A structure thereof is:

Silicone C=Monomethacryloxypropyl terminated polydimethylsiloxane. Astructure thereof is:

Tris=3-[Tris(trimethylsilyloxy)silyl]propyl methacrylate. A structurethereof is:

DMA=N,N-Dimethylacrylamide.

VMA=N-Vinyl-N-methylacetamide.

MMA=Methyl methacrylate.

HEMA=hydroxyethyl methacrylate.

EGMA=Ethylene glycol methyl ether methacrylate.

EGDMA=Ethylene glycol dimethacrylate.

TEGDMA=Tri(ethylene glycol)dimethacrylate.

TEGDVE=Tri(ethylene glycol)divinyl ether.

VAZO® 64=2,2′-Azobiz(isobutyronitrile).

UV 416=Cyasorb UV-416 from Cytec,2-(4-benzoyl-3-hydroxyphenoxy)ethylacrylate.

VPB=4-vinylphenyl boronic acid.

PBS=phosphate buffered saline (20 mM, pH=7.3).

NaCMC=Sodium Carboxymethyl Cellulose.

PEI 25K=Poly(ethyleneimine) solution Mw ˜2500.

PVOH=polyvinyl alcohol (such as, for example, MOWIOL® series polyvinylalcohol, Kuraray, Houston, Tex., USA, including MOWIOL® 4-88 (MW=31K),MOWIOL® 8-88 (67K), MOWIOL® 18-88 (130K), MOWIOL® 40-88 (127K), MOWIOL®40-88 (205K); PVOH 98-99% (MW=146-186K), PVOH 96% (85-124K), PVOH 87-89%(13-23K), PVOH 87-89% (31-50K), PVOH 87-89% (85-124K), 87-89%(146-186K)).

JEFFAMINE® ED-600 polyetheramine=an aliphatic polyether diamine derivedfrom a propylene oxide-capped polyethylene glycol (Huntsman Corporation,The Woodlands, Tex., USA).

PVP 1300K=Polyvinylpyrrolidone Mw ˜1300K

MPC=2-methacryloyloxyethyl phosphorylcholine (Lipidure®, NOFCorporation, Tokyo, Japan).

VB6=VAT Blue 6 (7,16-Dichloro-6,15-dihydroanthrazine-5,9,14,18-tetrone).

Preparation of Contact Lenses

Polymerizable lens compositions were prepared by mixing variouscombinations of the ingredients and components as indicated by some ofthe tables below. The lens formulations were formed into lenses in thefollowing general manner.

Contact lens molds were injection molded from non-polar polypropyleneresin using conventional injection molding techniques and equipment.Each contact lens mold included a female mold member that includes aconcave optical quality surface for forming the front surface of thecontact lens, and a male mold member that includes a convex opticalquality surface for forming the back surface of the contact lens. Thefemale mold member can be understood to be a front surface mold, and themale mold member can be understood to be a back surface mold.

An amount (about 60 μl) of the polymerizable lens composition was placedon the concave surface of the female mold member. The male mold memberwas placed in contact with the female mold member such that thepolymerizable lens composition was located in a contact lens shapedcavity formed between the concave surface of the female mold member andthe convex surface of the male mold member. The male mold member washeld in position by an interference fit between a peripheral region ofthe female and male mold members.

The contact lens mold containing the polymerizable lens composition wasthen placed in an oven where the polymerizable lens composition wascured at a temperature of about 100° C. for about 30 minutes. Aftercuring, the contact lens mold contained a polymerized contact lensproduct within the contact lens shaped cavity.

The contact lens mold was removed from the oven and allowed to cool toroom temperature (about 20° C.). The contact lens mold was mechanicallydemolded to separate the male and female mold members from each other.The polymerized contact lens product remained attached to the male moldmember.

The polymerized contact lens product was then mechanically delensed fromthe male mold member to separate the contact lens product from the malemold member.

The separated contact lens product was then sealed in borate buffersaline solution in a blister package to form a packaged hydrated contactlens. The lenses in the blister were sterilized by autoclaving inaqueous solutions. The aqueous solutions used in autoclaving can includewetting agents under evaluation.

Methods for Characterizing Lens Products

Water Break Up Time (WBUT). Prior to testing, a lens is soaked in 3 mlof fresh PBS for at least 24 hours. Immediately before testing, the lensis shaken to remove excess PBS, and the length of time in seconds thatit takes for the water film to recede from the lens surface isdetermined (e.g., water break up time (water BUT, or WBUT)).

Advancing Contact Angle/Receding Contact Angle. The advancing contactangle can be determined using routine methods known to persons ofordinary skill in the art. For example, the advancing contact angles andreceding contact angles of the contact lenses provided herein can bemeasured using a captive bubble method. Advancing and receding watercontact angles of silicone hydrogel contact lenses can be determinedusing a Kruss DSA 100 instrument (Kruss GmbH, Hamburg), and as describedin D. A. Brandreth: “Dynamic contact angles and contact anglehysteresis”, Journal of Colloid and Interface Science, vol. 62, 1977,pp. 205-212 and R. Knapikowski, M. Kudra: Kontaktwinkelmessungen nachdem Wilhelmy-Prinzip-Ein statistischer Ansatz zur Fehierbeurteilung”,Chem. Technik, vol. 45, 1993, pp. 179-185, and U.S. Pat. No. 6,436,481,all incorporated in their entireties herein by reference.

As an example, the advancing contact angle and receding contact anglecan be determined using a captive bubble method using phosphate bufferedsaline (PBS; pH=7.2). Prior to testing, the lens is soaked in pH 7.2 PBSsolution for at least 30 minutes or overnight. The lens is flattenedonto a quartz surface and rehydrated with PBS for 10 minutes beforetesting. An air bubble is placed onto a lens surface using an automatedsyringe system. The size of the air bubble can be increased anddecreased to obtain the receding angle (the plateau obtained whenincreasing the bubble size) and the advancing angle (the plateauobtained when decreasing the bubble size).

Static Contact Angle. Static Contact Angle can be determined usingroutine methods known to persons of ordinary skill in the art. Forexample, the Static Contact Angle can be determined using a captivebubble method, or using a DSA 100 drop shape analysis system (Kruss,Hamburg, Germany). Prior to testing, the lens is soaked in pH 7.2 PBSsolution for at least 30 minutes or overnight.

Modulus. The modulus of a lens body can be determined using routinemethods known to persons of ordinary skill in the art. For example,pieces of a contact lens having about 4 mm width can be cut out from acentral part of a lens, and modulus (unit; MPa) can be determined froman initial slope of a stress-strain curve obtained by the tensile testat the rate of 10 mm/min in air at a humidity of at least 75% at 25° C.,using an Instron 3342 (Instron Corporation, Norwood, Mass., USA).

PVOH Uptake. PVOH uptake from blister solutions can be determined, forexample, by gel permeation chromatography (GPC) after the lenses areplaced in a blister solution containing a PVOH solution at roomtemperature (RT) for a prescribed period of time, for example, 48 hours.

Ionoflux. The ionoflux of the lens bodies of the present lenses can bedetermined using routine methods known to persons of ordinary skill inthe art. For example, the ionoflux of a contact lens or lens body can bemeasured using a technique substantially similar to the “IonofluxTechnique” described in U.S. Pat. No. 5,849,811. For example, the lensto be measured can be placed in a lens-retaining device, between maleand female portions. The male and female portions include flexiblesealing rings which are positioned between the lens and the respectivemale or female portion. After positioning the lens in the lens-retainingdevice, the lens-retaining device is placed in a threaded lid. The lidis screwed onto a glass tube to define a donor chamber. The donorchamber can be filled with 16 ml of 0.1 molar NaCl solution. A receivingchamber can be filled with 80 ml of deionized water. Leads of theconductivity meter are immersed in the deionized water of the receivingchamber and a stir bar is added to the receiving chamber. The receivingchamber is placed in a thermostat and the temperature is held at about35° C. Finally, the donor chamber is immersed in the receiving chamber.Measurements of conductivity can be taken every 2 minutes for about 20minutes, starting 10 minutes after immersion of the donor chamber intothe receiving chamber. The conductivity versus time data should besubstantially linear.

Tensile Strength. The tensile strength of a lens body can be determinedusing routine methods known to persons of ordinary skill in the art. Forexample, pieces of a contact lens having about 4 mm width can be cut outfrom a central part of a lens, and tensile strength (unit; MPa) can bedetermined from testing using an Instron 3342 (Instron Corporation,Norwood, Mass., USA).

Elongation. The elongation of a lens body can be determined usingroutine methods known to persons of ordinary skill in the art. Forexample, the elongation (%) can be determined using an Instron 3342(Instron Corporation, Norwood, Mass., USA).

Oxygen Permeability (Dk). The Dk of the present lenses can be determinedusing routine methods known to persons of ordinary skill in the art. Forexample, the Dk value can be determined using a modified polargraphicmethod, as described in A single-lens polarographic measurement ofoxygen permeability (Dk) for hypertransmissible soft contact lenses, M.Chhabra et al., Biomaterials 28 (2007) 4331-4342.

Equilibrium Water Content (EWC). The water content of the present lensescan be determined using routine methods known to persons of ordinaryskill in the art. For example, a hydrated silicone hydrogel contact lenscan be removed from an aqueous liquid, wiped to remove excess surfacewater, and weighed. The weighed lens can then be dried in an oven at 80°C. under a vacuum, and the dried lens can then be weighed. The weightdifference is determined by subtracting the weight of the dry lens fromthe weight of the hydrated lens. The water content (%) is the (weightdifference/hydrated weight)×100.

Center Thickness of Lens (CT). The CT can be determined using routinemethods known to persons of ordinary skill in the art. For example, theCT can be determined using a Rehder ET gauge (Rehder DevelopmentCompany, Castro Valley, Calif., USA).

Example 1

A series of contact lenses were prepared with the polymerizable lenscompositions as shown in Tables 1 and 2 below. Formulations wereprepared by combining the ingredients in the indicated unit parts basedon the weight of the ingredients in the formulation.

An evaluation was conducted of possible agents to use to attach to theboronic acid moiety present in the lens. Lenses containing apolymerizable agent with at least one boronic acid moiety, specificallyVPB in the formulation used, were prepared using the ingredients andamounts shown in Tables 1 and 2 below, and then autoclaved in aqueoussolutions of various compounds shown in Table 3, to determine which ofthe compounds would attach to the surface of the lenses. Sodiumcarboxymethyl cellulose (Na CMC), agar, glycerol, and polyvinyl alcohol(PVOH) were evaluated. Samples lenses 1-12 used Formulation 1, whereinthe lenses were autoclaved in 1.2 ml of the indicated solution. Samples13-16 used formulation Formulation 2, wherein the lenses were autoclavedin 2.4 ml of the indicated solution. In Table 3, data is reported fortwo consecutive tests performed on the same lens.

TABLE 1 Formulation: 1 unit parts (wt) SIGMA 20 Silicone C 25 DMA 20 VMA30 EGMA 5 TEGDMA 0.5 TEGDVE 0.6 Vazo 64 0.3 Linker (VPB) 3

TABLE 2 Formulation: 2 unit parts (wt) SIGMA 15 Silicone C 25 DMA 25 VMA30 EGMA 5 TEGDMA 0.5 TEGDVE 0.6 Vazo 64 0.3 Linker (VPB) 3

WBUT results for the prepared lenses autoclaved in the indicated testsolutions are set forth in Table 3 below.

TABLE 3 WBUT after WBUT after 1 week in Wt % Compound Initial brief PBSoriginal (w/w) in Test WBUT rinsing solution Sample Solution (seconds)(seconds) (seconds) 1 1% Na CMC 2, 2 0, 0 0, 0 2 0.1% Na CMC 1, 1 0, 00, 0 3 1% Agar 2, 2 0, 0 0, 0 4 0.1% Agar 1, 1 0, 0 0, 0 5 1% Glycerol0, 0 0, 0 0, 0 6 0.1% Glycerol 0, 0 0, 0 0, 0 7 1% Sucrose 0, 0 0, 0 0,0 8 0.1% Sucrose 0, 0 0, 0 0, 0 9 0.5% PVOH 20, 20 20, 20 20, 20 10 1%Glycerol/ 20, 20 20, 20 20, 20 PVOH (1:100) 11 0.1% Glycerol/ 15, 17 12,15 20, 20 PVOH (1:100) 12 1% Glycerol/Na 2, 2 0, 0 0, 0 CMC (1:100) 131% PEI 25K 1, 2 0, 0 0, 1 14 1% Jeffamine 1, 1 0, 0 0, 0 ED-600 poly-etheramine 15 0.5% PVP 1300K 1, 1 0, 0 1, 0 16 1% Lipidure ®-HM 0, 1 0,0 0, 0

Starches and other compounds with a structure where adjacent atoms havea hydroxyl group bonded to each of the atoms, such as vicinal diols andcompounds with a 1, 2 polyol structure, were expected to bind similarlyto the boronic acid moiety, but this was not found to be the case. Otherknown comfort and/or wettability enhancing agents, includingpolyetheramine, poly(vinyl pyrrolidone), and 2-methacryloyloxyethylphosphorylcholine (MPC) were evaluated as well and were found not toattach to the surface of the lenses. It was found that only thesolutions containing a polyhydric alcohol with a backbone comprising atleast three carbon atoms, the three carbon atoms bonded in a row as acarbon atom on the right, a carbon atom in the middle, and a carbon atomon the left, wherein one and only one hydroxyl group is bonded to thecarbon atom on the right and to the carbon atom on the left, and ahydroxyl group is not bonded to the carbon atom in the middle, producedwettable lenses. Without being bound by theory, it is believed that thisparticular structure of polyhydric alcohol, when placed in contact withsurfaces comprising forms of opthalmically acceptable acids, includingpolymerizable forms of boronic acid, binds unexpectedly well to thesesurfaces, resulting in these surfaces exhibiting and retaining goodwettability over extended time periods. In this study, a form of PVOH,which has such a structure, was found to produce wettable lens surfaceswhen used to treat lenses containing a polymerized boronic acid moiety.In these studies, the presence of a wettable lens surface was consideredto be an indication that the test compound (for this study, a polyhydricalcohol with a 1,3 polyol structure and which comprised at least 5pendant hydroxyl groups, specifically a form of PVOH) was present on thelens surfaces.

Example 2

A series of contact lenses were prepared with the polymerizable lenscompositions as shown in Table 6. A series of contact lenses wereprepared with the polymerizable lens compositions as shown in Table 4.Formulations were prepared by combining the ingredients in the indicatedunit parts. The amount of VPB is varied for purposes of this evaluation.

This study was conducted to evaluate the effect on water break-up time(WBUT) of concentration of a polymerizable agent with at least oneboronic acid moiety in lenses of similar formulations. The PBS(phosphate buffered saline) used was 20 mM, pH=7.3. One lens of eachtype was tested repeatedly at subsequent time points; data reported(e.g.: 5, 6) is for the first and second tests performed on the samelens. For the measurements of WBUT, after briefly washing the lens with5 ml PBS, the data for this time point were collected on the differentlenses and then the other time points. As to the test conditions of thelens tested in 1.2 mL PBS, lenses were placed in 1.2 ml PBS and shakenat 37° C. at a speed of 100 rpm. WBUT of the lenses was determined afterautoclaving and after shaking for 6, 12 and 24 hours. Lenses of allformulations were autoclaved in 2.4 ml of a 0.50% PVOH (MW 146K to 186K,87-89% hydrolyzed) solution in PBS.

TABLE 4 Formulation ID 3 (control) 4 5 6 7 1 2 unit unit unit unit unitunit unit parts parts parts parts parts parts parts Ingredient (wt) (wt)(wt) (wt) (wt) (wt) (wt) SIGMA 25 25 25 25 25 20 15 Silicone C 20 20 2020 20 25 25 Tris 0 0 0 0 0 0 0 DMA 5 5 5 5 5 20 25 VMA 38 38 38 38 38 3030 MMA 12 12 12 12 0 0 0 EGMA 0 0 0 0 12 5 5 TEGDMA 0 0 0 0 0 0.5 0.5TEGDVE 0.8 0.8 0.8 0.8 0.8 0.6 0.6 Vazo 64 0.3 0.3 0.3 0.3 0.3 0.3 0.3UV 416 0 0 0 0 0 0 0 VPB 0 1 2 3 3 3 3

TABLE 5 Formulation 3 (con- Properties trol) 6 7 1 2 Tensile 0.683 1.3151.315 0.673 ± 0.086 0.836 ± 0.157 Strength (MPa) Modulus 0.641 2.6250.612 0.675 ± 0.008 0.716 ± 0.010 (MPa) Dry — — 9.20 9.46 ± 0.22 11.0 ±0.41 Extract- ables (wt %) Ionoflux 3.52 — 5.85 2.55 ± 0.30 7.19 ± 0.49(mm²/min) EWC (wt %) 56.42 — 52.31 51.07 ± 0.70  56.13 ± 1.27  Lens — —— 15.7, 15.9, 13.7, 13.9, Diameter 15.9 13.8 (mm) Elongation — — — 223 ±10  213 ± 15  (%) CT (mm) — — — 0.134 ± 0.006 0.097 ± 0.002 Dk (barrers)— — — 54 — Initial — — 56.4 — — Advancing Contact Angle (degrees)Advancing — — 62.2 — — Contact Angle Lens — — — — clear, Appearancecolorless Delensing — — — — easy to Observations delens

TABLE 6 Time Points WBUT after WBUT after shaking in shaking in thirdWBUT after WBUT after second sample of sample of 1.2 ml briefly shakingin 1.2 1.2 ml fresh PBS fresh PBS for WBUT after washing lens ml freshPBS for another 6 hrs. another 12 hrs. autoclaving with 5 ml for 6 hrs.(12 hrs. total) (24 hrs. total) Formulation (seconds) PBS* (seconds)(seconds) (seconds) (seconds) 3 (control) 4, 6 1, 1 2, 1 0, 0 0, 04 >20, >20 — >20, >20 10, 15 10, 8  5 >20, >20 — >20, >20 >20, >20 18,15 6 >20, >20 >20, >20 >20, >20 >20, >20 18, 15 1 >20, >20— >20, >20 >20, >20 >20, >20

The lenses made from formulations containing a form of an ophthalmicallyacceptable acid (VPB, a polymerizable form of boronic acid) displayedgood initial surface wettability following autoclaving in 0.5% PVOHsolution, while the lenses made from formulations that did not containthe ophthalmically acceptable acid, VPB, did not show good initialsurface wettability following autoclaving in 0.5% PVOH solution. Aftershaking in fresh samples of PVOH-free PBS for 6 hours, the lenses madefrom formulations containing 1%, 2% and 3% VPB showed good wettability.While shaking for an additional 6 or 12 hours in fresh PVOH-free PBSdecreased the surface wettability of the lenses containing VPB, thelenses made from formulations containing 3% VPB still retained goodwettability at the end of the study.

Example 3

An in vitro kinetic study on the wettability of the formulation 1 wasconducted. Contact lenses were prepared with the lens formulation 1,which was described in Example 2. As a control, commercially availableBIOFINITY® contact lenses were used (CooperVision Inc., Pleasanton,Calif., USA). Formulation 1 lenses were packaged singly in 1.2 ml PBS(20 mM) with a 0.5% PVOH solution (made using MW=146K-186K PVOH 87-89%hydrolyzed, 99.9% purity), autoclaved (30 minutes, 121° C.), and kept atroom temperature for 2 days, then packaged singly in blisters using 3.6ml PBS (20 mM) per package. One lens was tested for the 24 hour tests.Two lenses were tested for the 48 hour test. All lenses were shaken at35° C. at a speed of 100 rpm in 3.6 ml PBS for the indicated time point.The test results are set forth in Table 7.

TABLE 7 Formulation ID and Time Point Formulation 1 Formulation 1 lenseslenses shaken another 24 hrs. Control shaken 24 in 3.6 ml fresh PBSshaken Property hrs. (48 hrs. total) 24 hrs. WBUT (seconds) 15 to 20 12to 15 Not tested Static Contact 35.6 35.3 35.7 Angle (degrees) AdvancingContact 47.4 50.1 46.5 Angle (degrees)

As shown by the results in Table 7, the static and advancing contactangles of lenses made from a formulation containing an ophthalmicallyacceptable acid, and which were contacted with a solution of a 1,3polyol with at least 5 pendant hydroxyl groups, were determined andfound to be approximately equivalent to the control, i.e., thecommercially available BIOFINITY® lenses.

Example 4

Contact lenses were prepared with the polymerizable lens compositions asshown in Table 8. The indicated base formulations were previouslydescribed in Example 2. This study was conducted to evaluate the effectof contacting solution concentration, the contacting solution comprisinga solution of a 1,3 polyol with at least 5 pendant hydroxyl groups, onthe wettability of lens formulations containing an ophthalmicallyacceptable acid when the lenses are autoclaved in the contactingsolution. For this study, the 1,3 polyol with at least 5 pendanthydroxyl groups used was PVOH with a weight average molecular weight of146K to 186K, 87-89% hydrolyzed. The lenses were placed in 3.6 ml PBSand shaken at 37° C. at a speed of 100 rpm. WBUT of the lenses wasdetermined after autoclaving and after shaking for 24 hours.

TABLE 8 Formulation 7 Test Conditions 7 WBUT after Lens autoclaved in2.4 ml of WBUT after shaking for 24 PVOH solution of indicatedautoclaving hours in 3.6 ml concentration in PBS (seconds) PBS (seconds)0.5% PVOH >20, >20 16, 17 0.25% PVOH >20, >20 15, 16 0.1% PVOH >20, >2010, 10 0.05% PVOH >20, >20 15, 14 0.01% PVOH >20, >20 5, 5

The lenses of formulation 7 autoclaved in all the concentrations of PVOHsolution showed good wettability initially after autoclaving. Aftershaking in PVOH-free PBS for 24 hours, the lenses that had beenautoclaved in 0.5% and 0.25% PVOH still showed acceptable wettability.

Example 5

Contact lenses were prepared with the polymerizable lens compositions asshown in Table 9. Lenses were prepared using polymerizable compositionformulations designated as Formulation 8 (control) and Formulation 9.Formulations were prepared by combining the ingredients in the indicatedunit part amounts.

The uptake and release of a 1,3 polyol with at least 5 pendant hydroxylgroups, specifically a form of PVOH, from a lens made from a formulationcomprising an ophthalmically acceptable acid, specifically apolymerizable form of an ophthalmically acceptable acid (VPB) wereevaluated.

TABLE 9 Formulation 8 (control) 9 Ingredient unit parts (wt) unit parts(wt) SIGMA 25 25 Silicone C 20 20 DMA 5 13 VMA 38 30 MMA 0 12 EGMA 12 0TEGDVE 0.8 0.8 Vazo 64 0.3 0.3 VPB 0 3

The resulting reaction products (lenses) were hydrated and autoclaved in20 ml of PBS. For the purposes of this experiment, the lenses weresubsequently soaked in PBS (20 ml) for 3 autoclave cycles (20 min. percycle) in order to remove any leachable materials from the lenses whichcould interfere with the analysis of PVOH by GPC chromatography. Formanufacturing purposes, the three additional autoclave cycles could beomitted, as could extraction with an organic solvent or a solution of anorganic solvent. Initially, three lenses processed as described abovewere soaked in 3 ml of 100 ppm PVOH solution in PBS (the form of PVOHused was MOWIOL® PVOH, 40-88 205K, 88% hydrolyzed). At each time pointof the study, the lenses were transferred into fresh 100 ppm PVOHsolution, and the concentration of the PVOH solution that the lenseswere transferred out of was quantified by GPC using a standard method.Based on the concentration of PVOH remaining present in the solutions atthe time points, the accumulated uptake of PVOH per lens was calculatedfor each time point.

The PVOH uptake by lenses of formulations 8 (control) (“▪”) and 9 (“♦”)are plotted in FIG. 3. As shown by the results in FIG. 3, the lensesmade using formulation 8 (control), without a polymerizable agent withat least one boronic acid moiety, were found to take up an average of7.1 μg PVOH/lens during the first day, and 0 μg PVOH/lens after thefirst day. As no additional PVOH was taken up by the lenses, only thedata for days 1 and 2 are included in the graph. The lenses made usingformulation 9, containing VPB as the ophthalmically acceptable acid,were found to continue to take up a 1,3 polyol with at least 5 pendanthydroxyl groups, specifically PVOH, from the solution over the 10 daysstudied. The lenses were found to take up an average of 17.9 μgPVOH/lens over the 10 days.

Example 6

Contact lenses were prepared with polymerizable lens compositions ofsamples Formulations 8 (control) and 9, such as described in Example 5.For purposes of this study, the PVOH release by lenses of formulations 8and 9 was evaluated.

Sixteen individually packaged lenses made using formulations 8 and 9were prepared. The lenses were soaked individually in a 5000 ppm PVOHsolution in PBS (the form of PVOH used was MOWIOL® PVOH, 40-88 205K, 88%hydrolyzed). The lenses were soaked for 7 days after autoclaving tofully saturate them with the 1,3 polyol with at least 5 pendant hydroxylgroups, in this experiment a form of PVOH. After soaking for 7 days, theindividual lenses were blotted to remove any additional solution, andwere transferred to 10 ml of PBS not containing a 1,3 polyol with atleast 5 pendant hydroxyl groups, and stored at 35° C. for the durationof the study. At each of the time points, a sample of the PBS wasremoved from each vial and analyzed using GPC. Any sample remainingafter the analysis was returned to the vials and the vials were returnedto storage at 35° C. until the next time point. The GPC analysis wasconducted using a standard method and calibration standards of 100 ppm,80.23 ppm, 51.03 ppm, 23.59 ppm, and 10.00 ppm PVOH were used.

The PVOH release by lenses of formulations 8 (“▪”) and 9 (“♦”) areplotted in FIG. 3. As shown in FIG. 3, the lenses made using formulation9 and 8 were both found to release an average of 5.9 μg PVOH/lens withinthe first two hours. The formulation 9 lenses released slightly morePVOH over the course of the study, but not a significant amount more.The Formulation 8 control lenses did not release additional PVOH duringthe later time points. The data from the lens uptake study has beenincluded on this plot to illustrate that the formulation 8 lensesessentially released all of the taken up PVOH during the first two hoursof the study (within the margin of error of the study), while, after atleast 8 hours, the formulation 9 lenses retained most of the taken upPVOH (an average of 17.9 μg PVOH/lens taken up less an average of 5.9 μgPVOH/lens released after 2 hours left an average of approximately 12 μgPVOH/lens remaining in or on the lenses after 2 hours).

Additionally, it was noted that the lenses made using formulation 9,which contained an ophthalmically acceptable acid, specifically apolymerizable form of boronic acid (VPB) and which were contacted by asolution of a 1,3 polyol with at least 5 pendant hydroxyl groups, werefound to be wettable, while the lenses made with formulation 8, whichdid not contain an ophthalmically acceptable acid but which had beencontacted by a solution of a 1,3 polyol with at least 5 pendant hydroxylgroups, were not found to be wettable.

Example 7

A series of contact lenses were prepared with the polymerizable lenscompositions, as shown in Table 10, using formulation 1, which wasdescribed in Example 2, as the base formulation. The lenses offormulation 1 were contacted with a series of solutions of 1,3 polyolswith at least 5 pendant hydroxyl groups, in this experiment a series ofPVOH solutions with varied hydrolysis percentages (mole %) at variedconcentrations, and the WBUT of the resulting lenses was evaluated.Lenses of formulation 1, as described in Example 2, were prepared andpackaged in 1.2 ml PBS containing the indicated type of PVOH at theindicated concentration, autoclaved, and maintained at room temperaturefor 2 days. The lens packages were then opened and the lenses weretransferred to 3.6 ml PVOH-free PBS, and shaken at a speed of 100 rpmand a temperature of 35° C. for the indicated amount of time. At theindicated time points, the water break up time for the lenses wasdetermined along with the static and advancing contact angles (bothdetermined using the Captive Bubble method).

TABLE 10 Static Advancing Contact Contact Release WBUT Angle Angle PVOHUsed Time Point (seconds) (degrees) (degrees) 0.5% PVOH, 24 hours 15 to20 35.6 47.4 98-99% hydrolyzed 0.5% PVOH, 48 hours 12 to 15 35.3 50.198-99% hydrolyzed 0.5% PVOH,  5 days 12 to 13 36.4 49.8 98-99%hydrolyzed 0.25% PVOH, 24 hours 15 to 20 35.5 72.5 98-99% hydrolyzed0.25% PVOH, 48 hours 10 to 13 38.4 62.0 98-99% hydrolyzed 0.25% PVOH,  5days 15 to 18 37.4 68.2 98-99% hydrolyzed 0.5% PVOH, 96% 24 hours 15 to20 38.4 60.8 hydrolyzed 0.5% PVOH, 96% 48 hours <8 35.5 60.7 hydrolyzed0.5% PVOH, 96%  5 days 13 to 16 36.2 68.3 hydrolyzed 0.25% PVOH, 96% 24hours >20  38.4 63.8 hydrolyzed 0.25% PVOH, 96% 48 hours <8 38.1 68.3hydrolyzed 0.25% PVOH, 96%  5 days 15 to 18 37.5 70.4 hydrolyzed

Use of all of the PVOH solutions evaluated with these lenses was foundto result in lenses that maintained good WBUTs and good static andadvancing contact angles for up to 5 days, suggesting the lensesremained ophthalmically wettable for the duration of the study.

Example 8

A series of contact lenses were prepared with the polymerizable lenscompositions using formulation 1, containing an ophthalmicallyacceptable acid, specifically the polymerizable form of boronic acidVPB. The lenses were contacted with solutions comprising a 1,3 polyolwith at least 5 pendant hydroxyl groups, specifically PVOH solutionswith varied average molecular weights, as shown in Table 11. The PVOHGrade listed in Table 11 includes the degree of hydrolysis (98% or 99%).Lenses of formulation 1, which is described in Example 2, were preparedand packaged in 1.2 ml PBS containing the indicated type PVOH at theindicated concentration, autoclaved, and maintained at room temperaturefor 3 days. The lens packages were then opened and the lenses wereeither tested to determine the WBUT or the advancing contact angle (bythe Captive Bubble method) of the lenses. Additional lenses weretransferred to 3.6 ml of PVOH-free PBS and shaken at a speed of 100 rpmand a temperature of 35° C. for 24 hours, at which time the WBUT andadvancing contact angle (by the Captive Bubble method) of the lenseswere determined.

TABLE 11 1 day soaking in 3 days soaking in 3 days soaking in PVOHfollowed 3 days soaking in PVOH followed 3 days soaking in PVOH followedby 0 hrs. PVOH followed by 0 hrs. PVOH followed by 24 hrs. PVOH soakingin PBS by 0 hrs. soaking in PBS by 24 hrs. soaking in PBS Soln. Adv.Contact soaking in PBS Adv. Contact soaking in PBS Adv. Contact PVOHPVOH Conc. Angle WBUT Angle WBUT Angle Source Grade MW (wt. %) (degrees)(seconds) (degrees) (seconds) (degrees) MOWIOL  4-98%  ~27k 0.50% 81.8 ±1.5 20, 3 79.8 ± 5.6 5, 5, 10 78.7 MOWIOL 10-98%  ~61k 0.50% 80.8 ± 0.118, 10, 5 74.8 ± 6.2 5, 7, 10 80.7 MOWIOL 20-98% ~125k 0.50% 80.6 ±0.2 >20, 22, 22 66.8 ± 1.1 25, 18, 30 68.4 ± 6.5 MOWIOL 28-99% ~145k0.50% 74.9 ± 1.6 20, 23, >20 71.1 ± 0.1 25, >20, 20 71.4 ± 2.6 MOWIOL56-98% ~195k 0.50% 82.0 ± 0.4 >20, >20, >20 59.5 ± 7.0 20, >20, 20 60.3± 8.6 Aldrich 98-99% 146k-186k 0.50% ND >20, >20, >20  57.8 ± 10.1 15 to20 ND

The average molecular weight of the form of PVOH was observed toinfluence the water break up time of the lenses, with the highermolecular weight forms resulting in lenses with longer WBUTs.

Example 9

A series of contact lenses were prepared with silicone-freepolymerizable lens compositions as shown in Table 12. Formulations wereprepared by combining the ingredients in the indicated unit parts.Silicone-free lens formulations were made with and without the additionof an ophthalmically acceptable acid, specifically a polymerizable formof boronic acid (VPB).

TABLE 12 Formulation 25 25 Ingredient unit parts (wt) unit parts (wt)HEMA 76.85 76.85 MPC 14.53 14.53 EGDMA 0.7 0.7 Vazo 64 0.46 0.46 VB67.76 7.76 VPB 0 3

An evaluation of the silicone-free lens formulations was conducted fortensile strength, modulus, elongation, and PVOH uptake. PVOH uptake fromblister solutions was determined by GPC after the lenses were placed in1.2 ml PBS blister solution containing 0.5% MOWIOL® 40-88 (MW ˜205 k) atroom temperature for 24 hours. The properties of the lenses made usingthe Table 12 formulations are shown in Table 13.

TABLE 13 Formulation ID Properties 24 25 Tensile Strength (MPa) 0.630.94 Modulus (MPa) 0.66 0.76 Elongation (%) 151 202 PVOH Uptake byLenses after 24 hrs.* (μg/lens) 33.1 190.6

The lenses made from the formulation containing an ophthalmicallyacceptable acid (VPB) took up significantly more PVOH from solutionafter sitting in the PVOH solution for 24 hours.

Example 10

A series of contact lenses were prepared with the polymerizable lenscompositions as shown in Tables 14 and 15. One set of formulations (10to 13) was more hydrophobic in nature as compared to the other set offormulations (14 to 17) as confirmed by the initial WBUT results for theformulations. The content of the ophthalmically acceptable acid (VPB) inboth sets of formulations was varied (0%, 1%, 2% and 3% VPB). The levelof uptake of the 1,3 polyol with at least 5 pendant hydroxyl groups(PVOH) over time was evaluated for each of the formulations.

TABLE 14 Hydrophobic Formulations 10 11 12 13 unit parts unit parts unitparts unit parts Ingredient (wt) (wt) (wt) (wt) SIGMA 20.0 20.0 20.020.0 Silicone C 25.0 25.0 25.0 25.0 VMA 30.0 30.0 30.0 30.0 DMA 20.020.0 20.0 20.0 EGMA 5.0 5.0 5.0 5.0 TEGDVE 0.6 0.6 0.6 0.6 TEGDMA 0.50.5 0.5 0.5 Vazo 64 0.3 0.3 0.3 0.3 VPB 0 1 2 3

TABLE 15 Hydrophilic Formulations 14 15 16 17 unit parts unit parts unitparts unit parts Ingredient (wt) (wt) (wt) (wt) SIGMA 20.0 20.0 20.020.0 Silicone C 25.0 25.0 25.0 25.0 VMA 40.0 40.0 40.0 40.0 DMA 5.0 5.05.0 5.0 EGMA 7.0 7.0 7.0 7.0 TEGDVE 0.6 0.6 0.6 0.6 TEGDMA 0.5 0.5 0.50.5 Vazo 64 0.5 0.5 0.5 0.5 VPB 0 1 2 3

The resulting lenses were demolded, delensed, and each lens was packedin an individual 20 ml glass vial. To hydrate the lenses, each vial wasfilled with 5 ml of PBS and allowed to hydrate for 30 minutes. Followinghydration, the vials and lenses received three flush cycles, each cycleconsisting of replacing the 5 ml of PBS with 5 ml of fresh PBS after thelens had sat in the PBS for 60 minutes.

PVOH uptake by the lenses was studied by combining 20 lenses of the sameformulation, wiping the surface water off each lens, and soaking the 20lenses in 10 ml of a 200 ppm PVOH solution in PBS. Each lens was addedindividually to the PVOH solution in order to prevent the lenses fromall sticking together. The PVOH solutions used were 200 ppm of MOWIOL®40-88 PVOH, MW approx. 205,000 Daltons, and 200 ppm of MOWIOL® 20-98PVOH, MW approx. 146,000 Daltons, as indicated. For the first time point(time 0), the 20 lenses were removed from the PVOH solution immediatelyafter the last lens had been added. The remaining samples were stored atRT until their indicated timepoints. For the remaining samples, at timepoints of 1 day, 2 days, 3 days, 7 days, 10 days, and 14 days, thelenses were transferred to a fresh sample of PVOH solution, and the oldPVOH solution was retained for GPC testing to determine the PVOHsolution concentration. The samples of PVOH solution were analyzed byGPC using a Ultrahydrogel linear column (Waters Corporation, Milford,Mass., USA), with a mobile phase of 90% 0.1M NaNO₃ in H₂O: 10% MeOH at aflow rate of 0.8 ml/min. with an injection volume of 200 μl, a columntemperature of 45° C., and a refractive index (RI) detector. Due tooverlap between one of the PVOH peaks with a leached linear polymerpeak, peak heights were used to quantitate the PVOH rather than peakareas. In addition to PVOH uptake, lens diameter and water break-up time(WBUT) were measured at times 0 and 14 days. The initial (time 0) WBUTwas measured in PBS; the day 14 lenses were transferred to PBS andstored in the PBS for 5 days prior to determining the WBUT. The valuesreported for lens diameter and WBUT in TABLES 16 and 17 are based on asample size of 5 lenses.

TABLE 16 Hydrophobic Formulations Time 0 Time 0 Time 0 Time 0 14 Days 14Days 14 Days 14 Days 10 11 12 13 10 11 12 13 Unit parts VPB 0 1   2  3   0   1   2 3  With 20-98 PVOH WBUT (sec) <8 10 to 13 13 to 16  9 to12 15 to 18 12 to 15 18 to 20 17 to 20 Diameter (mm) 14.58 14.57 14.4614.22 14.69 14.57 14.46  14.04 PVOH uptake 1.5 1.9 2.8 3.4 5.7 6.1 7.523.4 (μg/lens) With 40-88 PVOH WBUT (sec) 12 to 15 17 to 20 15 to 18 13to 16 15 to 18 13 to 16 >20 18 to 20 Diameter (mm) 14.66 14.59 14.4214.12 14.61 14.53 14.46  14.04 PVOH uptake 1.3 1.9 2.6 3.6 3.9 5.7 6.420.1 (μg/lens)

TABLE 17 Hydrophilic Formulations Time 0 Time 0 Time 0 Time 0 14 Days 14Days 14 Days 14 Days 14 15 16 17 14 15 16 17 Unit parts VPB 0   1 2 3  0   1   2 3  With 20-98 PVOH WBUT (sec) n/d n/d n/d n/d 17 to 20 12 to15 18 to 20 15 to 18 Diameter (mm) n/d n/d n/d n/d 15.44 15.33 15.09 14.60 PVOH uptake 1.0 1.7 2.3 1.3 8.5 7.7 7.1 11.6 (μg/lens) With 40-88PVOH WBUT (sec) 15 to 18 >20 >20 15 to 18 18 to 20 18 to 20 >20 18 to 20Diameter (mm) 15.29 15.14 15.06 14.71 15.53 15.33 15.10  14.66 PVOHuptake 1.1 1.6 2.1 2.5 4.6 3.4 7.6 11.2 (μg/lens)

The rate of uptake of the two forms of PVOH evaluated (the MOWIOL® 20-98PVOH and the MOWIOL® 40-88 PVOH) are shown for the hydrophobicformulations (10 to 13) and for the hydrophilic formulations (14 to 17)in FIGS. 4 to 7. With both forms of PVOH, the total amount of PVOH takenup by the lenses after the initial time point was greater for thehydrophobic formulations. While higher levels of VPB content in theformulations was generally observed to result in higher levels of PVOHbeing taken up by the lenses, the total uptake results were not linearlyconcentration-dependent for the hydrophobic formulations with eitherform of PVOH, or for the hydrophilic formulation with the 20-98 PVOH.For the hydrophobic formulation tested with the 40-88 PVOH, the totaluptake of PVOH was linearly concentration-dependent based on the VPBconcentration present in the formulation. The uptake of PVOH by lensesof formulations containing 2 unit parts or less VPB appeared to reachsteady state between approximately 100 and 150 hours, while theformulations containing 3 parts VPB generally required 250 hours or moreto reach steady state.

Example 11

A series of contact lenses were prepared with the polymerizable lenscompositions as shown in Table 18. In these formulations, differenttypes of ophthalmically acceptable acids, specifically different formsof polymerizable ophthalmically acceptable acids, were used. Theophthalmically acceptable acids used in these formulations include4-Vinylphenylboronic acid (VPB, Alfa Aesar, Ward Hill, Mass., USA),3-Vinylphenylboronic acid (3-VPB, Sigma-Aldrich, Atlanta, Ga., USA),3-methacrylamidophenylboronic acid (MAPBA, Combi-Blocks Inc., San Diego,Calif., USA), and 3-Acrylamidophenylboronic acid (AAPBA, FrontierScientific Inc., Logan, Utah, USA). The resulting lenses formed fromthese polymerizable lens compositions were contacted with a 1,3 polyolwith at least 5 pendant hydroxyl groups, for this experiment, a solutionof 0.5% MOWIOL® 20-98 PVOH. After polymerizing the polymerizable lenscompositions comprising an ophthalmically acceptable acid and contactingthem with the 1,3 polyol with at least 5 pendant hydroxyl groups, thelenses were washed with 5 ml of PBS.

TABLE 18 Formulation 18 19 20 21 unit parts unit parts unit parts unitparts Ingredient (wt) (wt) (wt) (wt) SiGMA 20 20 20 20 Silicone C 25 2525 25 VMA 30 30 30 30 DMA 20 20 20 20 EGMA 5 5 5 5 TEGDVE 0.6 0.6 0.60.6 TEGDMA 0.5 0.5 0.5 0.5 VASO 64 0.3 0.3 0.3 0.3 VPB 3 0 0 0 MAPBA 0 30 0 AAPBA 0 0 3 0 3-VPB 0 0 0 3

TABLE 19 Formulation ID Properties 18 19 20 21 Tensile Strength (MPa)0.689 ± 0.006 0.577 ± 0.14 0.635 ± 0.047 0.746 ± 0.080 Modulus (MPa)0.619 ± 0.010  0.628 ± 0.010 0.766 ± 0.088 0.791 ± 0.042 Elongation (%)226 ± 20  165 ± 37 164 ± 24  173 ± 17  Diameter (mm) 13.1 13.6 13.5 13.3Initial WBUT in PBS before contacting with 0 to 2 0 to 2 0 to 2 0 to 2PVOH solution (seconds) WBUT after contacting with PVOH >20 10 to15 >20 >20 solution (seconds) WBUT after contacting with PVOH solutionand >20 0 to 2 >20 >20 after washing with 5 ml PBS (seconds)

The MAPBA purchased from Combi-Blocks appeared to be of very low purityas the raw material was a solid chunk of material that was orange-red incolor, rather than a white powder as expected. For this reason, it isbelieved that the Formulation 19 lenses actually contained far less than3 unit parts of MAPBA, which in turn resulted in the lenses notexhibiting good wettability when contacted with the PVOH solution andnot retaining good wettability after being contacted with the PVOHsolution and subsequently being washed with the PBS. All of the otherlenses made from polymerizable compositions comprising a polymerizableform of an ophthalmic acid, specifically a polymerizable form of boronicacid, exhibited good wettability after being contacted with the 1,3polyol with at least 5 pendant hydroxyl groups (in this experiment,PVOH), and retained good wettability after subsequently being washedwith PBS.

Example 12

A series of contact lenses were prepared with the polymerizable lenscompositions as shown in Table 20. The properties of the resultinguncomplexed lenses bodies formed from these polymerizable compositionsare shown in Table 21.

TABLE 20 Formulation 22 23 Ingredient unit parts (wt) unit parts (wt)Silicone C 40 — Silicone A — 14 Silicone B — 29 HEMA 3.5 — NVP — 43 VMA40 — DMA 4 — EGMA (Ethylene glycol 6 7 methyl ether methacrylate) EGDMA(Ethylene glycol 0.2 — dimethacrylate) EHMA (2-Ethylhexyl — 7methacrylate) TEGDMA (Tri(ethylene — 0.1 glycol) dimethacrylate) TEGDVE(Tri(ethylene — 0.4 glycol) divinyl ether) VASO 64 0.5 0.3 VPB 2 0Norbloc 0.9 0.9 RB 247 0.01 0.01

TABLE 21 Formulation ID Properties 22 23 Advancing Contact Angle(degrees) 64.2 ± 3.7  48.2 ± 1.5 by captive bubble Modulus (MPa) 0.76 ±0.02  0.70 ± 0.04 Ionoflux (×10⁻³ mm²/min.) 2.38 ± 0.10  3.67 ± 0.15Equilibrium Water Content 50.31 ± 0.44  48.80 ± 0.52 (percent) bygravimetric method Elongation (%) 302 ± 7  309 ± 63 Tensile Strength(MPa) 1.36 ± 0.04  0.99 ± 0.27

Following demolding and delensing, the uncomplexed lens bodies offormulation 23 were contacted using complexing solutions comprisingvarious polyhydric alcohols comprising 1, 2 diol or 1,3 diol moieties ina TRIS-EDTA buffer solution, as shown in Table 22.

The TRIS-EDTA buffer solution comprised 0.82% wt/wt sodium chloride,0.023% wt/wt Tris(hydroxymethyl)aminomethane, 0.125% wt/wtTris(hydroxymethyl)aminomethane hydrochloride, 0.37% wt/wtEthylenediaminetetraacetic acid sodium salt dehydrate, and 0.005% wt/wtpolysorbate 80 in deionized water, pH 7.1 to 7.5, Osmolarity 275±25mOsM. All buffer components except the deionized water were obtainedfrom Sigma-Aldrich (Atlanta, Ga., USA), and all buffer solutioncomponents except the polysorbate 80 were reagent grade materials.

The polyhydric alcohol comprising 1, 2 diol or 1,3 diol moieties usedfor this example was PVOH. Solutions of 1% MOWIOL® 40-88 PVOH or of 1%MOWIOL® 8-88 PVOH in the TRIS-EDTA buffer were prepared. For onesolution with each form of PVOH, the pH of the solution was unadjusted,while for one solution with each form of PVOH the pH was adjusted to pH10. The lens bodies were first hydrated in de-ionized water, and placedin the TRIS-EDTA and PVOH solutions for 30 minutes, transferred to freshde-ionized water for 30 minutes, and then again transferred to freshde-ionized water before being placed in a blister package with theTRIS-EDTA buffer solution (without PVOH), and autoclaved for 20 minutesat 121° C. The advancing contact angle of the hydrated uncomplexed(control) and complexed lens bodies were determined using the captivebubble method after equilibrating the lens bodies in PBS for at least 6hours.

TABLE 22 Reduction from % Formulation ID Lens 1 Lens 2 Averageuncomplexed Reduction Form. 23 in 60.3° 60.1° 60.2° DI H₂0 (uncomplexed)Form. 23 in 49.4° 49.0° 49.2° 11.0° 18.3% 1% 40-88 (complexed) Form. 23in 54.2° 50.3° 52.3° 7.9° 13.1% 1% 40-88 pH 10 (complexed) Form. 23 in48.4° 51.0° 49.7° 10.5° 17.4% 1% 8-88 (complexed) Form. 23 in 49.9°47.9° 48.9° 11.3° 18.8% 1% 8-88 pH 10 (complexed)

Based on the averaged values for the two lenses tested for eachcomplexing solution comprising a TRIS-EDTA buffer system and PVOH, thecomplexed lens bodies had advancing contact angles ranging from about13% to about 19% lower than the advancing contact angle of theuncomplexed lens bodies. The complexing solution comprising a TRIS-EDTAbuffer system and PVOH did not gel during the course of the study.

Applicant specifically incorporates the entire contents of all citedreferences in this disclosure. Further, when an amount, concentration,or other value or parameter is given as either a range, preferred range,or a list of upper preferable values and lower preferable values, thisis to be understood as specifically disclosing all ranges formed fromany pair of any upper range limit or preferred value and any lower rangelimit or preferred value, regardless of whether ranges are separatelydisclosed. Where a range of numerical values is recited herein, unlessotherwise stated, the range is intended to include the endpointsthereof, and all integers and fractions within the range. It is notintended that the scope of the invention be limited to the specificvalues recited when defining a range.

Other embodiments of the present invention will be apparent to thoseskilled in the art from consideration of the present specification andpractice of the present invention disclosed herein. It is intended thatthe present specification and examples be considered as exemplary onlywith a true scope and spirit of the invention being indicated by thefollowing claims and equivalents thereof.

What is claimed is:
 1. A method of manufacturing a hydrogel contact lensbody, comprising: providing a lens body comprising at least one form ofboronic acid, boronic ester, boronic anhydride or combination thereof;and contacting the lens body with a contacting solution comprising atleast one form of tris(hydroxymethyl)aminomethane (TRIS), and a form ofpoly(vinyl alcohol) (PVOH), wherein the at least one form of TRIS ispresent in the solution at a concentration effective to prevent gelationof the form of PVOH.
 2. The method of claim 1, wherein the at least oneform of the boronic acid, boronic ester, boronic anhydride orcombination thereof is a boronic acid having the structure:


3. The method of claim 1, wherein the hydrogel lens body is apolymerized reaction product of a polymerizable composition, thepolymerizable composition comprising at least one hydrophilic monomer,and at least one crosslinking agent; and the polymerized reactionproduct is a polymer formed of polymerized units of the at least onehydrophilic monomer, and crosslinks formed by the at least onecrosslinking agent.
 4. The method of claim 1, wherein the at least oneform of TRIS comprises a TRIS buffer system comprising at least one formof tris(hydroxymethyl)aminomethane (TRIS), and at least one form ofethylenediaminetetraacetic acid (EDTA).
 5. The method of claim 1,wherein the contacting solution further comprises a tonicity adjustingagent.
 6. The method of claim 1, wherein the contacting solution has anosmolarity from about 100 mOsm to about 400 mOsm.
 7. The method of claim1, wherein the contacting solution further comprises at least onesurfactant.
 8. The method of claim 1, wherein the at least one form ofTRIS is present in the contacting solution at a concentration effectiveto lower an effective pKa of boronic acid moieties present on at least asurface of the lens body.
 9. The method of claim 1, wherein the step ofcontacting the lens body with the contacting solution further comprisescomplexing at least a portion of boronic acid moieties present in thelens body with at least a portion of PVOH moieties present in solution.10. The method of claim 1, wherein the step of contacting the lens bodywith the contacting solution comprises soaking the lens body in thecontacting solution, rinsing the lens body with the contacting solution,or both soaking and rinsing the lens body.
 11. The method of claim 1,wherein the step of contacting the lens body with the contactingsolution comprises placing the lens body in a contact lens package withthe solution, sealing the package, and sterilizing the package.
 12. Themethod of claim 11, wherein the at least one form of TRIS is present inthe solution at a concentration effective to prevent gelation of theform of PVOH over a shelf life of the sterilized package.
 13. A methodof treating a hydrogel contact lens comprising: (i) providing a contactlens comprising at least one form of boronic acid, boronic ester,boronic anhydride or combination thereof; (ii) prior to the contact lensbeing worn by a user, contacting the lens body with a first contactingsolution comprising at least one form of tris(hydroxymethyl)aminomethane(TRIS) and a form of poly(vinyl alcohol) (PVOH), wherein the at leastone form of TRIS is present in the solution at a concentration effectiveto prevent gelation of the form of PVOH; and (iii) subsequently to thecontact lens being worn by the user, contacting the lens body with asecond contacting solution comprising at least one form of TRIS.
 14. Themethod of claim 13, wherein the at least one form of TRIS of the firstcontacting solution is the same as the at least one form of TRIS of thesecond contacting solution.
 15. A hydrogel contact lens product,comprising: (i) a lens body comprising at least one form of boronicacid, boronic ester, boronic anhydride or combination thereof; (ii) apackaging solution comprising at least one form oftris(hydroxymethyl)aminomethane (TRIS) and a form of poly(vinyl alcohol)(PVOH), wherein the at least one form of TRIS is present in the solutionat a concentration effective to prevent gelation of the form of PVOH fora duration of time equivalent to a shelf life of a sterilized contactlens package; (iii) a contact lens package base member with a cavityconfigured to hold the lens body and the packaging solution; and (iv) aseal attached to the base member configured to maintain the lens bodyand the packaging solution in a sterile condition for the duration oftime equivalent to the shelf life of the sterilized contact lenspackage.
 16. The hydrogel contact lens product of claim 15, wherein theat least one form of TRIS is present in the packaging solution at aconcentration effective to lower an effective pKa of boronic acidmoieties present on at least a surface of the lens body.
 17. Thehydrogel contact lens product of claim 15, wherein at least a portion ofboronic acid moieties present on at least a surface of the lens body arecomplexed with at least a portion of PVOH moieties present in thepackaging solution.
 18. The method of claim 1, wherein the concentrationof TRIS is from about 0.01% to about 10%.
 19. The method of claim 13,wherein the concentration of TRIS is from about 0.01% to about 10%. 20.The hydrogel contact lens product of claim 15, wherein the concentrationof TRIS is from about 0.01% to about 10%.